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List of Papers
Takeshi Mori Last modified date：2024.04.01

Associate Professor / laboratory of functional organization chemistry / Department of Applied Chemistry / Faculty of Engineering


Papers
1. S. Li, H. Toriumi, D. Takahashi, T. Kamasaki, Y. Fujioka, S. Nagatoishi, J. Li, Y. Liu, T. Hosokawa, K. Tsumoto, Y. Ohba, Y. Katayama, D. Murakami, K. Hase, T. Mori, Safe and efficient oral allergy immunotherapy using one-pot-prepared mannan-coated allergen nanoparticles, Biomaterials, 303, 122381, 2023.11.
2. Y. Niidome, K. Nakamura, S. Qi, S. Ito, B. Yu, Y. Nagai, N. Tanaka, T. Mori, Y. Katayama, T. Fujigaya, T. Shiraki,, Near infrared photoluminescent detection of serum albumin based on selective recognition with a long-chain fatty acid tethered on locally functionalized single-walled carbon nanotubes, Carbon, 2023.10.
3. R. Shiraki, K. Wakigawa, S. Ogawa, A. Gohda, T. Mori, Y. Katayama, First GC/MS identification of aqueous ammonia: utilization of ethenesulfonyl fluoride as a selective and rapid derivatization reagent of ammonia in aqueous media, Anal. Method., 15, 5294-5299, 2023.09.
4. K. Kodama, C. Tateishi, T. Oda, L. Cui, K. Kuramoto, H. Yahata, K. Okugawa, S. Maenohara, H. Yagi, M. Yasunaga, I. Onoyama, K. Asanoma, T. Mori, Y. Katayama, K. Kato, Development of novel tracers for sentinel node identification in cervical cancer, Cancer Sci., 114, 4216-4224, 2023.06.
5. A. Kishimura, K.C. Biplab, T. Nii, T. Mori, Y. Katayama, Dynamic frustrated charge hotspots created by charge density modulation sequester globular proteins into complex coacervates,, Chem. Sci., 14, 6608-6620, 2023.04.
6. S. Li, D. Murakami, S. Nagatoishi, K. Tsumoto, Y. Katayama, T. Mori, One-pot preparation of mannan-coated antigen nanoparticles using human serum albumin as a matrix for tolerance induction, J. Coll. Interf. Sci., 649, 955-965, 2023.04.
7. A. Ahmad, T. Maruyama, T. Nii, T. Mori, Y. Katayama, A. Kishimura, Facile preparation of hexagonal nanosheets via polyion complex formation from α-helical polypeptides and polyphosphate-based molecules, Chem. Commun., 59, 1657-1660, 2023.04.
8. K. Tanito, T. Nii, Y. Yokoyama, H. Oishi, M. Shibata, S. Hijii, R. Kaneko, C. Tateishi, S. Ito, A. Kishimura, T. Mori, Y. Katayama, Engineered macrophages acting as a trigger to induce inflammation only in tumor tissues based on arginase 1-responsive TNF-α accelerated release, J. Controlled Release, 361, 885-895, 2023.04.
9. C. Tateishi, A. Koga, A. Matsuura, R. Kaneko, K. Tanito, T. Nii, Akihiro Kishimura, T. Mori, Y. Katayama, A human cell orthogonal enzyme β-D-galacturonidase for sensitive detection of antigen proteins, Analyst, 148, 2237-2244, 2023.04.
10. R. Saeki, S. Kobayashi, R. Shimazui, T. Nii, A. Kishimura, T. Mori, M. Tanaka, Y. Katayama, Characterization of polypropyleneimine as an alternative transfection reagent,, Anal. Sci., 2023.02.
11. Y. Liu, A. Kishimura, Y. Katayama, T. Mori, Development of Polynucleotide-loaded Nanoparticles for the Regulation of Intracellular Nucleotide Levels, Chem. Lett. , 51, 1037-1039, 2022.10.
12. K. Yakabe, S. Higashi, M. Akiyama, H. Mori, T. Murakami, A. Toyoda, Y. Sugiyama, S. Kishino, K. Okano, A. Hirayama, A. Gotoh, S. Li, T. Mori, T. Katayama, J. Ogawa, S. Fukuda, K. Hase, and Y.-G. Kim, Dietary-protein sources modulate host susceptibility to Clostridioides difficile infection through the gut microbiota, Cell Rep., 40, 111332, 2022.10.
13. T. Hosokawa, S. Tanaka, T. Mori, Y. Baba, and Y. Katayama, Quiescent B cells acquire sensitivity to cell cycle arresting agents by B cell receptor stimulation, Biol. Pharm. Bull., 45, 847-850, 2022.10.
14. H. Feng, J.-H. Kang, S. Qi, A. Kishimura, T. Mori, Y. Katayama, Preparation of a PEGylated liposome that co-encapsulates L-arginine and doxorubicin to achieve a synergistic anticancer effect, RSC Adv., 11, 34101-34106, 2022.06.
15. Asmariah Ahmad, Teruki Nii, Takeshi Mori, Yoshiki Katayama, Masanori Toyofuku, Akihiro Kishimura, Nanostructure Control of an Antibiotic-Based Polyion Complex Using a Series of Polycations with Different Side-Chain Modification Rates., Macromolecular rapid communications, 10.1002/marc.202200316, e2200316, 2022.06, Developing nanovehicles for delivering antibiotics is a promising approach to overcome the issue of antibiotic resistance. This study aims to utilize a polyion complex (PICs) system for developing novel nanovehicles for polymyxin-type antibiotics, which are known as last resort drugs. The formation of antibiotic-based PIC nanostructures is investigated using colistimethate sodium (CMS), an anionic cyclic short peptide, and a series of block catiomers bearing different amounts of guanidinium moieties on their side chains. In addition, only the modified catiomer, and not the unmodified catiomer, self-assembles with CMS, implying the importance of the guanidine moieties for enhancing the interaction between the catiomer and CMS via the formation of multivalent hydrogen bonding. Moreover, micellar and vesicular PIC nanostructures are selectively formed depending on the ratio of the guanidine residues. Size-exclusion chromatography reveals that the encapsulation efficiency of CMS is dependent on the guanidinium modification ratio. The antimicrobial activity of the PIC nanostructures is also confirmed, indicating that the complexation of CMS in the PICs and further release from the PICs successfully occurs..
16. K. Tanito, Y. Oshiro, H. Tagawa, A. Kishimura, T. Mori, Y. Katayama, Comparative evaluation of natural killer cell-mediated cell killing assay based on the leakage of an endogenous enzyme or a pre-loaded fluorophore, Anal. Sci., 37, 1571-1575, 2021.12.
17. S. Li, K. Yakabe, K. Zai, Y. Liu, A. Kishimura, K. Hase, Y.-G. Kim, T. Mori, Y. Katayama, Specific adsorption of a β-lactam antibiotic in vivo by an anion-exchange resin for protection of the intestinal microbiota, Biomater. Sci., 9, 7219-7227, 2021.11.
18. J. Li, Y. Mu, Y. Liu, A. Kishimura, T. Mori, Y. Katayama, Effect of size and loading of retinoic acid in polyvinyl butyrate nanoparticles on amelioration of colitis, polymers, 13, 1472, 2021.08.
19. C. W. Kim, R. Toita, J.-H. Kang, T. Mori, A. Kishimura, Y. Katayama, Protein kinase C α-responsive gene carrier for cancer-specific transgene expression and cancer therapy, ACS Biomater. Sci. Eng., 7, 2530-2537, 2021.06.
20. Y. Liu, T. Maruyama, Biplab KC, T. Mori, Y. Katayama, A. Kishimura, Inducible Dynamic Behavior of Polyion Complex Vesicles by Disrupting Charge Balance, Chem. Lett., 50, 1034-1037, 2021.04.
21. K. Sasaki, K. Muguruma, R. Osawa, A. Fukuda, A. Taniguchi, A. Kishimura, Y. Hayashi, T. Mori, Y. Katayama, Synthesis and biological evaluation of a monocyclic Fc-binding antibody-recruiting molecule for cancer immunotherapy, RSC Med. Chem., 12, 406-409, 2021.02.
22. K. Sasaki, M. Harada, T. Yoshikawa, H. Tagawa, Y. Harada, Y. Yonemitsu, T. Ryujin, A. Kishimura, T. Mori, Y. Katayama, Fc-binding antibody-recruiting molecules targeting prostate-specific membrane antigen: defucosylation of antibody for efficacy improvement,, ChemBioChem, 22, 496-500, 2021.02.
23. Y. Mu, Y. Kinashi, J. Li, T. Yoshikawa, A. Kishimura, M. Tanaka, T. Matsui, T. Mori, K. Hase, Y. Katayama, Polyvinyl butyrate nanoparticles as butyrate donors for colitis treatment, ACS Applied Bio Mater., 4, 2335, 2021.01.
24. Y. Mu, Y. Kinashi, A. Kishimura, T. Mori, K. Hase, Y. Katayama, Effect of polyvinyl butyrate nanoparticles incorporated with immune suppressing vitamins on alteration of population of intestinal immune cells, Prog. Nat. Sci. Mater. Int., 30, 707-70, 2020.12.
25. X. Sun, R. Tokunaga, Y. Nagai, R. Miyahara, A. Kishimura, S. Kawakami, Y. Katayama, T. Mori, Ligand design for specific MHC class I molecules on the cell surface, Biochemistry, 59, 4646, 2020.10.
26. H. Feng, A. Kishimura, T. Mori, Y. Katayama, Evaluation of Synergistic Effect of L-Arginine on the Anticancer Activity of Doxorubicin by Using Co-culture System, Anal Sci, 36, 1279-1283, 2020.09.
27. Md. Z. Hosain, F. Hyodo, T. Mori, K. Takahashi, Y. Nagao, H. Eto, T. Nakaji, M. Murata, T. Akaboshi, M. Matsuo, Y. Katayama, Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism, Sci. Rep, 10, 16489, 2020.08.
28. Y. Mu, J. Li, J.-H. Kang, H. Eto, K. Zai, A. Kishimura, F. Hyodo, T. Mori, Y. Katayama, A lipid-based nanocarrier containing active vitamin D3 ameliorates NASH in mice via direct and intestine-mediated effects on liver inflammation, Biol. Pharm. Bull., 43, 1413-1420, 2020.06.
29. H. Feng, L. T. Nam, T. Yoshikawa, A. Kishimura, T. Mori, Y. Katayama, Effect of an endothelin B receptor agonist on the tumor accumulation of nanocarriers, Biol. Pharm. Bull., 43, 1301-1305, 2020.06.
30. K. Yuzuriha, K. Yakabe, H. Nagai, S. Li, T. Zendo, K. Zai, A. Kishimura, K. Hase, Y-G Kim, T. Mori, Y. Katayama, Protection of gut microbiome from antibiotics: development of a vancomycin-specific adsorbent with high adsorption capacity, Biosci. Microbio. Food Health, 39, 128-136, 2020.06, 腸内細菌叢を破壊することが知られる抗生物質（バンコマイシン）を腸間で特異的に吸着する粒子を開発し、実際に、腸内細菌を保護することを示した。また細菌叢の破壊に由来する感染症からマウスを保護することができた。.
31. K. Yuzuriha, A. Yoshida, S. Li, A. Kishimura, T. Mori, Y. Katayama, Synthesis of peptide conjugates with vitamins for induction of antigen-specific immunotolerance, J. Peptide Sci., 26, e3275, 2020.06.
32. K. Noguchi, T. Shimomura, Y. Ohuchi, M. Ishiyama, M. Shiga, T. Mori, Y. Katayama, Y. Ueno, Β-galactosidase-catalyzed fluorescent reporter labeling of living cells for sensitive detection of cell surface antigens, Bioconjugate Chem., 31, 1740-1744, 2020.05, beta-ガラクトシダーゼを酵素として、一細胞の抗原を高感度に増感検出する方法（蛍光がターンオンし、細胞に共有結合して脱離しない）の開発に初めて成功した。.
33. T. Ryujin, T. Shimizu, R. Miyahara, D. Asai, R. Shimazui, T. Yoshikawa, A. Kishimura, T. Mori, T. Ishida, Y. Katayama, Blood retention and antigenicity of polycarboxybetaine-modified liposomes, Int. J. Pharm. , 586, 119521, 2020.04.
34. K. Sasaki, M. Harada, Y. Miyashita, H. Tagawa, A. Kishimura, T. Mori, Y. Katayama,, Fc-binding antibody-recruiting molecules exploit endogenous antibodies for anti-tumor immune responses, Chem. Sci., 11, 3208-3214, 2020.03, 抗体医薬を低分子化合物で置き換えることを企図し、がん細胞と内在性の抗体を架橋する低分子を開発した。この分子は、in vitro, in vivoで抗がん活性を示した。.
35. H. Tagawa, K. Maruyama, K. Sasaki, N. Konoue, A. Kishimura, M. Kanai, T. Mori, K. Oisaki, Y. Katayama, Induction of ADCC by folic acid-mAb conjugate prepared by tryptophan-selective reaction toward folate-receptor-positive cancer cells, RSC Adv., 10, 16727-16731, 2020.03.
36. T. Yoshikawa, K. Q. Phan, H. Tagawa, K. Sasaki, H. Feng, A. Kishimura, T. Mori, Y. Katayama, Modification of nitric oxide donors onto a monoclonal antibody boosts accumulation in solid tumors, Int. J. Pharm., 583, 119352, 2020.03.
37. 穆 云妹, 李 晋廷, Zai Khadijah, 岸村 顕広, 兵藤 文紀, 森 健, 片山 佳樹, ビタミンD3含有脂質ナノ粒子によるリーキーガットの改善に基づくNASHの治療(Therapeutic effect of lipid-based nanocarriers containing vitamin D3 on NASH by ameliorating the leaky gut), 日本薬学会年会要旨集, 140年会, 27X-pm12S, 2020.03.
38. T. Nobori, M. Kawamura, R. Yoshida, T. Joichi, K. Kamino, A. Kishimura, E. Baba, T. Mori, Y. Katayama,, Fluorescence Signal Amplification by Using β-Galactosidase for Flow Cytometry; Advantages of an Endogenous Activity-free Enzyme,, Anal. Chem., 92, 3069-3076, 2020.01.
39. T. Mori, Y. Katayama, Signal amplification in flow cytometry for cell surface antigen analysis, J. Biochem., 166, 205-212, 2019.12.
40. D. Asai, T. Fukuda, K. Morokuma, D. Funamoto, Y. Yamaguchi, T. Mori, Y. Katayama, K. Shibayama, H. Nakashima, Injectable polypeptide hydrogel depot system for assessment of the immuneresponse-inducing efficacy of sustained antigen release alone, Macromol. Biosci., 19, e1900167, 2019.10.
41. T. Mori, A. Kishimura, Y. Katayama, , Nanoparticle-Based Drug and Gene Delivery for Tumor Targeting, Material Matters, 14.3, 2019.10.
42. W. Hatanaka, H. Takeuchi, M. Koga, T. Ryujin, A. Kishimura, Y. Katayama, S. Tsukiji, T. Mori, Synthesis of Transmembrane Molecules by Click Chemistry, Chem Lett, 48, 433-436, 2019.06.
43. K. Zai, N. Ishihara, H. Oguchi, M. Hirota, T. Mori, K. Hase, Y. Katayama, Regulation of inflammatory response of macrophages and induction of regulatory T cells by using retinoic acid-loaded nanostructured lipid carrier, Anal. Sci., 30, 1-11, 2019.06.
44. H. Nagai, W. Hatanaka, M. Matsuda, A. Kishimura, Y. Katayama, T. Mori, Folate receptor-specific cell-cell adhesion by using a folate-modified peptide-based anchor, J. Biomater. Sci. Polym. Ed., 30, 983-993, 2019.06.
45. T. Yoshikawa, Y. Mori, H. Feng, K. Q. Phan, A. Kishimura, J.-H. Kang, T. Mori, Y. Katayama, Rapid and continuous accumulation of nitric oxide-releasing liposomes in tumors to augment the enhanced permeability and retention (EPR) effect, Int. J. Pharm., 565, 481-487, 2019.06.
46. K. Zai, K. Yuzuriha, A. Kishimura, T. Mori, Y. Katayama, Preparation of complexes between ovalbumin nanoparticles and retinoic acid for efficient induction of tolerogenic dendritic cells, Anal. Sci., 34, 1243-1248, 2018.12.
47. K. Zai, M. Hirota, T. Yamada, N. Ishihara, T. Mori, A. Kishimura, K. Suzuki, K. Hase, Y. Katayama, Therapeutic effect of vitamin D3-containing nanostructured lipid carriers on inflammatory bowel disease, J. Controlled Release, 286, 94-102, 2018.11.
48. H. Sato, Y. Miyashita, K. Sasaki, A. Kishimura, T. Mori, Y. Katayama, Non-covalent Coating of Liposome Surface with IgG through Its Constant Region, Chem. Lett., 47, 770-772, 2018.10.
49. K. Sasaki, Y. Miyashita, D. Asai, D. Funamoto, K. Sato, Y. Yamaguchi, Y. Mishima, T. Iino, S. Takaishi, J. Nagano, A. Kishimura, T. Mori, Y. Katayama, A Peptide Inhibitor of Antibody-Dependent Cell-Mediated Cytotoxicity against EGFR/Folate Receptor-α Double Positive Cells, Med. Chem. Commun., 9, 783-788, 2018.03.
50. T. Nobori, K. Tosaka, A. Kawamura, T. Joichi, K. Kamino, A. Kishimura, E. Baba, T. Mori, Y. Katayama, Alkaline Phosphatase-Catalyzed Amplification of a Fluorescence Signal for Flow Cytometry, Anal. Chem., 90, 1059-1062, 2018.02, フローサイトメトリーを高感度化するために、酵素反応を利用して細胞に対する蛍光標識の強度を増強させる方法を開発した.
51. E. Nakahei, K. Takehara, H. Sato, K. Zai, A. Kishimura, T. Mori, Y. Katayama, A Dual Alkylated Peptide-ligand Enhances Affinity to Human Serum Albumin, Anal. Sci., 34, 501-504, 2018.01.
52. H. Sato, E. Nakhaei, Elnaz, T. Kawano, M. Murata, A. Kishimura, T. Mori, Y. Katayama, Ligand-mediated Coating of Liposomes with Human Serum Albumin, Langmuir, 34, 2324-2331, 2018.01.
53. E. Nakhaei, C. W. Kim, D. Funamoto, H. Sato, Y. Nakamura, A. Kishimura, T. Mori, Y. Katayama, Ligand design for cancer imaging with long blood circulation and enhanced accumulation ability in tumors, Med. Chem. Commun., 8, 1190-1195, 2017.09.
54. Y. Tahara, T. Yoshikawa, H. Sato, Y. Mori, Z. Hosain, A. Kishimura, T. Mori, Y. Katayama, Encapsulation of a nitric oxide-donor into a liposome to boost the enhanced permeation and retention (EPR) effect, Med. Chem. Commun., 8, 415-421, 2017.08.
55. Hengmin Tang, Yuki Sakamura, Takeshi Mori, Yoshiki Katayama, Akihiro Kishimura, Development of Enzyme Loaded Polyion Complex Vesicle (PICsome): Thermal Stability of Enzyme in PICsome Compartment and Effect of Coencapsulation of Dextran on Enzyme Activity., Macromolecular bioscience, 10.1002/mabi.201600542, 17, 8, 2017.08, Applications of enzymes are intensively studied, particularly for biomedical applications. However, encapsulation or immobilization of enzymes without deactivation and long-term use of enzymes are still at issue. This study focuses on the polymeric vesicles "PICsomes" for encapsulation of enzymes to develop a hecto-nanometer-scaled enzyme-loaded reactor. The catalytic activity of a PICsome-based enzyme nanoreactor is carefully examined to clarify the effect of compartmentalization by PICsome. Encapsulation by PICsome provides a stability enhancement of enzymes after 24 h incubation at 37 °C, which is particularly helpful for maintaining the high effective concentration of β-galactosidase. Moreover, to control the microenvironment inside the nanoreactor, a large amount of dextran, a neutral macromolecule, is encapsulated together with β-galactosidase in the PICsome. The resulting dextran-coloaded nanoreactor contributes to the enhancement of enzyme stability, even after exposure to 24 h incubation at -20 °C, mainly due to the antifreezing effect..
56. Enzyme-catalyzed amplification of fluorescent immunolabeling of a single cell for high-sensitive flow cytometry.
57. Md Zahangir Hosain, Kazuki Yuzuriha, Khadijah, Masafumi Takeo, Akihiro Kishimura, Yoshihiko Murakami, Takeshi Mori, Yoshiki Katayama, Synergic modulation of the inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine-containing polymer-lipid hybrid nanoparticles., MedChemComm, 10.1039/c7md00174f, 8, 7, 1514-1520, 2017.07, Inflammatory activation of macrophages is a key factor in chronic inflammatory diseases such as ulcerative colitis. The excessive production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) by macrophages causes oxidative stress during the inflammatory response and exaggerates inflammatory lesions in ulcerative colitis. Inhibition of the inflammatory activation of macrophages is a promising treatment for chronic inflammatory diseases. Here, we prepared self-filling polymer-lipid hybrid nanoparticles (PST-PLNPs) consisting of poly dl-lactic acid as a hydrophobic biodegradable polymer core encapsulating α-tocopherol (T) and phosphatidylserine (PS) both on the surface and interior of the particle. We confirmed the anti-inflammatory response of these hybrid nanoparticles in activated murine macrophages. PS has anti-inflammatory effects on macrophages by modulating the macrophage phenotype, while α-tocopherol is an antioxidant that neutralizes ROS. We found that PS-containing (PS-PLNPs) and PS plus α-tocopherol-containing (PST-PLNPs) polymer-lipid hybrid nanoparticles significantly increased the viability of lipopolysaccharide (LPS)-treated macrophages compared with phosphatidylcholine-containing PLNPs. PST-PLNPs had a better effect than PS-PLNPs, which was attributed to the synergy between PS and α-tocopherol. This synergic action of PST-PLNPs reduced NO and pro-inflammatory cytokine (IL-6) production and increased anti-inflammatory cytokine (TGF-β1) production when incubated with activated macrophages. Thus, these self-filling biodegradable polymer-lipid hybrid nanoparticles (PST-PLNPs) containing anti-oxidant and anti-inflammatory molecules might be potential alternative drug carriers to liposomes and polymeric nanoparticles for the treatment of chronic inflammatory diseases such as ulcerative colitis..
58. A. Tsuchiya, J.-H. Kang, T. Mori, Y. Naritomi, S. Kushio, T. Niidome, K. Tachibana, Y. Takahashi, Y. Negishi, Y. Oda, R. Suzuki, K. Maruyama, Y. Katayama, Efficient delivery of signal-responsive gene carriers for disease-specific gene expression via bubble liposomes and sonoporation, , Coll. Surf. B: Biointerfaces, 160, 60-64, 2017.06.
59. E. Nakhaei, C. W. Kim, D. Funamoto, H. Sato, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Ligand design for cancer imaging with long blood circulation and enhanced accumulation ability in tumors, Med. Chem. Comm., 2017.05.
60. Y. Nakamura, H. Sato, T. Nobori, H. Matsumoto, S. Toyama, T. Shuno, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Modification of ligands for serum albumin on polyethyleneimine to stabilize polyplexes in gene delivery, J. Biomater. Sci. Polym. Ed., 2017.05.
61. C. Li, M. Takeo, M. Matsuda, H. Nagai, S. Xizheng, W. Hatanaka, Akihiro Kishimura, Yoshiki Katayama, Takeshi Mori, Facilitating the presentation of antigen peptides on dendritic cells for cancer immunotherapy using a polymer-based synthetic receptor, Med. Chem. Commun., 2017.05.
62. W. Hatanaka, M. Kawaguchi, X. Sun, Y. Nagao, H. Ohshima, M. Hashida, Y. Higuchi, Akihiro Kishimura, Yoshiki Katayama, Takeshi Mori, Use of membrane potential to achieve transmembrane modification with an artificial receptor, Bioconjugate Chem., 28, 296, 2017.03, 細胞膜に膜貫通した状態で分子を修飾する方法を世界ではじめて開発した。.
63. Takeshi Mori, Yoshiki Katayama, Akihiro Kishimura, Y. Tahara, Encapsulation of a nitric oxide-donor into a liposome to boost the enhanced permeation and retention (EPR) effect, Med. Chem. Commun, 8, 415, 2017.01.
64. K. Naoyama, Takeshi Mori, Yoshiki Katayama, Akihiro Kishimura, Fabrication of Dendrimer‐Based Polyion Complex Submicrometer‐Scaled Structures with Enhanced Stability under Physiological Conditions, Macromol. Rapid Commun., 37, 1087, 2016.05.
65. Kim CW, Asai D, Kang JH, Kishimura A, Mori T, Katayama Y, Reversal of efflux of an anticancer drug in human drug-resistant breast cancer cells by inhibition of protein kinase Cα (PKCα) activity., Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 10.1007/s13277-015-3963-4, 37, 2, 1901-8, 2016.02.
66. P. Kumar, M. Z. Hosain, J.-H. Kang, M. Takeo, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Suppression of atopic dermatitis in mice model by reducing inflammation utilizing phosphatidylserine-coated biodegradable microparticles, J. Biomater. Sci. Polym. Ed., 26, 1465, 2015.11.
67. E. K. Lee, C. W. Kim, H. Kawanami, Akihiro Kishimura, T. Niidome, Takeshi Mori, Yoshiki Katayama, Utilization of a PNA-peptide Conjugate to Induce a Cancer Protease-Responsive RNAi Effect, RSC Adv., 5, 85816, 2015.11, PNA-peptideコンジュゲートにより、腫瘍において選択的にRNAiを生じるシステムを開発した。腫瘍で高活性化しているcathepsin Bを標的にしたシステムであるが、一般性が高く、望みのプロテアーゼに対して設計可能である。.
68. S. Sugimoto, R. Moriyama, Takeshi Mori, Y. Iwasaki, Surface engineering of macrophages with nucleic acid aptamers for circulating tumor cell capture, Chem. Commun., 51, 17428, 2015.11.
69. K. Li, H. Sato, C.W. Kim, Y. Nakamura, G.X. Zhao, D. Funamoto, T. Nobori, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection, J. Biomater. Sci. Polym. Ed., 26, 657, 2015.07.
70. Kai Li, Hikari Sato, Chan Woo Kim, Yuta Nakamura, Guo Xi Zhao, Daiki Funamoto, Takanobu Nobori, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection, Journal of Biomaterials Science, Polymer Edition, 10.1080/09205063.2015.1054922, 26, 11, 657-668, 2015.07, We synthesized polymeric gene carriers consisting of poly-L-lysine (PLL) main chain modified both with substrate peptide for protein kinase C (PKC) and alkanethiol (pentadecanethiol). Due to the grafted substrate peptide, the polyplex prepared from these carriers is expected to show gene expression triggered by the phosphorylation of the peptide by intracellular PKC. The modified alkanethiol on the main chain stabilized the polyplex both via disulfide crosslinking and hydrophobic interaction. The polyplex found to show gene expression in vitro when the alkanethiol content in the main chain was enough low (4-mol%-modification of PLLs ε-amine group) to minimize cytotoxic effect. Even though the content of alkanethiol is low, the polyplex had significant stability in a model serum solution and showed longer blood circulation in vivo. The polyplex clearly accumulated in tumor after intravenous injection..
71. Masafumi Takeo, Cuicui Li, Masayoshi Matsuda, Hiroko Nagai, Wataru Hatanaka, Tatsuhiro Yamamoto, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Optimum design of amphiphilic polymers bearing hydrophobic groups for both cell surface ligand presentation and intercellular cross-linking, Journal of Biomaterials Science, Polymer Edition, 10.1080/09205063.2015.1007414, 26, 6, 353-368, 2015.04, Amphiphilic polymers bearing hydrophobic alkyl groups are expected to be applicable for both ligand presentation on the cell surface and intercellular crosslinking. To explore the optimum design for each application, we synthesized eight different acyl-modified dextrans with varying molecular weight, alkyl length, and alkyl modification degree. We found that the behenate-modified polymers retained on the cell surface longer than the palmitate-modified ones. Since the polymers were also modified with biotin, streptavidin can be presented on the cell surface through biotin-streptavidin recognition. The duration of streptavidin on the cell surface is longer in the behenate-modified polymer than the palmitate-modified one. As for the intercellular crosslinking, the palmitate-modified polymers were more efficient than the behenate-modified polymers. The findings in this research will be helpful to design the acyl-modified polymers for the cell surface engineering..
72. M. Takeo, C. Li, M. Matsuda, H. Nagai, W. Hatanaka, T. Yamamoto, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Optimum design of amphiphilic polymers bearing hydrophobic groups both for cell surface ligand presentation and intercellular cross-linking, J. Biomater. Sci. Polym. Ed., 26, 353, 2015.03.
73. D Funamoto, D Asai, CW Kim, Y Nakamura, EK Lee, T Niidome, Takeshi Mori, Yoshiki Katayama, Tandemly Repeated Peptide for Cancer-specific Gene Carrier Prepared by Native Chemical Ligation, Chem Lett, 44, 474-476, 2015.02.
74. D. Funamoto, D. Asai, K. Sato, Y. Yamaguchi, C. W. Kim, H. Sato, E. Nakhaei, S. Matsumoto, T. Yoshikawa, K. Sasaki, T. Yamamoto, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Antibody Internalization into Living Cell via Crosslinker-mediated Endocytosis, Chem. Lett., 44, 468, 2015.02.
75. Daiki Funamoto, Daisuke Asai, Kazuki Sato, Yoko Yamaguchi, Chan Woo Kim, Hikari Sato, Elnaz Nakhaei, Shingo Matsumoto, Takuma Yoshikawa, Koichi Sasaki, Tatsuhiro Yamamoto, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Antibody internalization into living cells via crosslinker-mediated endocytosis, Chemistry Letters, 10.1246/cl.141157, 44, 4, 468-470, 2015.01, We reported here an alternative strategy of antibody internalization by crosslinker-mediated endocytosis. This cross-linker consists of IgG binding peptide and folic acid as cancer targeting ligands toward the folate receptor, which highly expresses in many cancer cells surface. This crosslinker successfully facilitated antibody internalization into cancer cell by the folate receptor-mediated endocytosis..
76. Shunsuke Sugimoto, Rui Moriyama, Takeshi Mori, Yasuhiko Iwasaki, Surface engineering of macrophages with nucleic acid aptamers for the capture of circulating tumor cells, Chemical Communications, 10.1039/c5cc06211j, 51, 98, 17428-17430, 2015.01, In order to enhance the interactions between macrophages and cancer cells, thiol-terminated nucleic acid aptamers were immobilized on methacryloyl-functionalised carbohydrates of macrophages. The adhesion of cancer cells on the surface modified macrophages was significantly accelerated..
77. Daiki Funamoto, Daisuke Asai, Chan Woo Kim, Yuta Nakamura, Eun Kyung Lee, Takanobu Nobori, Takuro Niidome, Takeshi Mori, Yoshiki Katayama, Tandemly repeated peptide for cancer-specific gene carrier prepared by native chemical ligation, Chemistry Letters, 10.1246/cl.141121, 44, 4, 474-476, 2015.01, We reported here a preparation of a cancer-specific gene carrier by native chemical ligation of a substrate peptide of protein kinase Cα (PKCα), which highly expresses in many types of cancer. This carrier is a tetramer of the substrate peptide connected with adequate spacer to maintain reactivity toward PKCα. The carrier successfully regulated the reporter gene expression responding to the phosphorylation of its serine residues..
78. Eun Kyung Lee, Chan Woo Kim, Hiroyuki Kawanami, Akihiro Kishimura, Takuro Niidome, Takeshi Mori, Yoshiki Katayama, Utilization of a PNA-peptide conjugate to induce a cancer protease-responsive RNAi effect, RSC Advances, 10.1039/c5ra17737e, 5, 104, 85816-85821, 2015.01, Small interfering RNA (siRNA) is regarded as a promising tool for cancer therapy because of the wide applicability to various cancer-related genes. However, non-specific delivery of siRNA is one of the major causes of adverse effects. To access the issue, here we designed a new siRNA system which turns on RNAi responding to a cancer cell-specific protease, cathepsin B. The system uses a peptide nucleic acid (PNA)-peptide conjugate to provide this protease-responsive activation. The PNA-peptides were found to form hybrids with double-stranded RNAs with complementary protruding regions, which then affected the susceptibility of dsRNA to Dicer. The dsRNA/PNA-peptide hybrids were activated in cancer cells with a high cathepsin B activity to show RNAi..
79. Masayoshi Matsuda, Wataru Hatanaka, Masafumi Takeo, Chan Woo Kim, Takuro Niidome, Tatsuhiro Yamamoto, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Short peptide motifs for long-lasting anchoring to the cell surface, Bioconjugate Chemistry, 10.1021/bc500465j, 25, 12, 2134-2143, 2014.12, A rational design strategy has been developed for the construction of stable peptide-based anchors for the efficient modification of cell surfaces. Six types of peptide composed of five residues with divalent hydrophobic groups have been designed using this new strategy. Among them, a peptide with a sequence of NBD-Lys-Lys(X)-Lys-Lys-Lys(X)-NH2 (NBD: fluorophore, Lys(X): N-ε-palmitoyl-L-lysine) was found to show the highest modification efficacy and longevity in culture medium. The good performance of this peptide was attributed to (1) its high aqueous solubility, which allowed it to partition from the medium to the cell surface, and (2) the high binding affinity of the saturated palmitoyl groups to the cell membrane. We found that the distribution of the peptide was affected by recycling endosome, which enabled the representation of the peptide following its endocytotic disappearance from the cell membrane. Biotin was also presented on the cell surface using this peptide-based anchor to examine its recognition by streptavidin. The efficacy of the recognition process increased as the length of the oligoethylene glycol spacer increased, indicating that it was necessary for the biotin tag to move away from the membrane glycoproteins on the cell surface to facilitate its efficient recognition by streptavidin. (Figure Presented)..
80. Riki Toita, Jeong Hun Kang, Chan Woo Kim, Shujiro Shiosaki, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Effect of peptide content on the regulation of transgene expression by protein kinase Cα-responsive linear polyethylenimine-peptide conjugates, Colloids and Surfaces B: Biointerfaces, 10.1016/j.colsurfb.2014.09.004, 123, 123-129, 2014.11, We examined a series of linear polyethylenimine (LPEI)-based nanocarriers that activate transgene expression in response to cancer-specific protein kinase Cα (PKCα). Eight types of LPEI-peptide conjugate differing in peptide content and number were synthesized using click chemistry. The conjugates could form polyplexes with pDNA through electrostatic interaction, but the degree of pDNA condensation, sizes, and surface charges of the resulting polyplexes depended on the pendant-peptide content and number. None of the polyplexes showed significant cytotoxicity toward human hepatoma cells (HepG2). Furthermore, pendant peptide content and number markedly affected transgene activation in response to PKCα. To achieve an all-or-none response to PKCα, we determined the optimum peptide content and number in LPEI-peptide conjugates as ≈6. mol% and ≈40. peptides/conjugate..
81. Takuro Niidome, Hisayo Yamauchi, Kayo Takahashi, Kenshiro Naoyama, Kazuto Watanabe, Takeshi Mori, Yoshiki Katayama, Hydrophobic cavity formed by oligopeptide for doxorubicin delivery based on dendritic poly(L-lysine), Journal of Biomaterials Science, Polymer Edition, 10.1080/09205063.2014.938979, 25, 13, 1362-1373, 2014.09, To deliver anti-cancer drugs to tumors, a hydrophobic cavity was prepared in the dendritic molecule, dendritic poly(L-lysine) of sixth generation (KG6), which was used as a drug carrier. The dendritic molecule was modified with polyethylene glycol (PEG)-linked hydrophobic penta-phenylalanine or penta-Alanine. The hydrophobic cavity was formed between the KG6 and PEG chains. The penta-phenylalanine peptide was better in encapsulating doxorubicin (DOX) in the cavity compared with penta-Alanine. The loaded DOX was slowly released from the cavity, and it depended on pH. After intravenous injection, the DOX-loaded dendrimers accumulated in the tumor by the enhanced permeability and retention effect, and showed significant suppression of tumor growth without loss of body weight. These results indicate that hydrophobic oligopeptides can be used for forming a hydrophobic cavity in a dendritic molecule for delivery of anti-cancer drugs to tumor sites..
82. Takuro Niidome, Risa Gokuden, Kazuto Watanabe, Takeshi Mori, Tatsuya Naganuma, Hideo Utsumi, Kazuhiro Ichikawa, Yoshiki Katayama, Nitroxyl radicals-modified dendritic poly(l -lysine) as a contrast agent for Overhauser-enhanced MRI, Journal of Biomaterials Science, Polymer Edition, 10.1080/09205063.2014.943538, 25, 13, 1425-1439, 2014.09, Overhauser-enhanced magnetic resonance imaging (OMRI), which is a double resonance technique, creates images of free radical distribution in animals by enhancing the water proton signal intensity by the overhauser effect. In this study, we constructed a contrast agent by combining PROXYL groups that have nitroxyl radicals with PEG-modified dendritic poly(l-lysine) that accumulates in the tumor by enhanced permeability and retention (EPR) effect. Addition of the PROXYL groups at the PEG chains termini on KG6 was advantageous in OMRI, because the ESR signal of the nitroxyl radical was maintained without decay caused by mobility restriction, even if the PROXYL groups were attached at 25 mol% on one molecule. After intramuscular injection of the molecule modified at 25 mol%, that is, PR25-PEG-KG6, a significant OMRI signal was observed at the injected site. However, no signal was detected in the tumor after intravenous injection of PR25-PEG-KG6 to a tumor-bearing mouse, although PR 25-PEG-KG6 itself accumulated in the tumor. The reason was that the nitroxyl radicals were immediately reduced in the blood after the injection, suggesting that use of stable nitroxyl radicals will enable detection of tumors by OMRI after intravenous injection..
83. K Tobinaga, C Li, M Takeo, T Niidome, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Rapid and serum-insensitive endocytotic delivery of proteins using biotinylated polymers attached via multivalent hydrophobic anchors, J. Controlled Release, 177, 27, 2014.08.
84. T. Niidome, N. Chijiiwa, T. Yamasaki, K. Yamada, Takeshi Mori, T. Naganuma, H. Utsumi, H. Utsumi, Yoshiki Katayama, Change in Overhauser Effect-enhanced MRI Signal in Response to uPA Highly Expressing in Tumor, Chem Lett, 43, 999, 2014.08.
85. M. Matsuda, W. Hatanaka, M. Takeo, C. W. Kim, T. Niidome, T. Yamamoto, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Short Peptide Motifs for Long-Lasting Anchoring to the Cell Surface, Bioconjugate Chem., 25, 2134, 2014.08.
86. GX Zhao, H Tanaka, CW Kim, K Li, D Funamoto, T Nobori, Y Nakamura, T Niidome, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Histidinylated poly-L-lysine-based vectors for cancer-specific gene expression via enhancing the endosomal escape, J. Biomater. Sci. Polym. Ed., 25, 519, 2014.07.
87. H. Sato, Y. Nakamura, E. Nakhaei, D.Funamoto, C. W. Kim, T. Yamamoto, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, A liposome reversibly coated with serum albumin, Chem. Lett., 43, 1481, 2014.06.
88. H. Ikeda, Y. Yayama, A. Hata, J. Kamimotoa, T. Yamamoto, Takeshi Mori, Yoshiki Katayama, PNA-tagged peptide microarrays for ratiometric activity detection of cellular protein kinases, Anal. Sci., 30, 631, 2014.05.
89. T. Nobori, S. Shiosaki, Takeshi Mori, R. Toita, C. W. Kim, Y. Nakamura, A. Kishimura, T. Niidome, Yoshiki Katayama, A fluorescent polyion complex nanoparticle that incorporates an internal standard for quantitative analysis of protein kinase activity, Bioconjugate Chem., 25, 869, 2014.05.
90. T. Yamamoto, Takeshi Mori, Yoshiki Katayama, Microarray Technologies for Intracellular Kinome Analysis, Current Med. Chem., 21, 2542, 2014.05.
91. Takanobu Nobori, Shujiro Shiosaki, Takeshi Mori, Riki Toita, Chan Woo Kim, Yuta Nakamura, Akihiro Kishimura, Takuro Niidome, Yoshiki Katayama, Fluorescent polyion complex nanoparticle that incorporates an internal standard for quantitative analysis of protein kinase activity., Bioconjugate chemistry, 10.1021/bc500142j, 25, 5, 869-72, 2014.05, We demonstrate a polyion complex (PIC) nanoparticle that contains both a responsive fluorophore and an "internal standard" fluorophore for quantitative measurement of protein kinase (PK) activity. The PK-responsive fluorophore becomes more fluorescent with PK-catalyzed phosphorylation of substrate peptides incorporated in the PIC, while fluorescence from the internal standard remains unchanged during phosphorylation. This new concept will be useful for quantitative PK assays and the discovery of PK inhibitors..
92. Mohamed R. Berber, Inas H. Hafez, Keiji Minagawa, Takeshi Mori, A sustained controlled release formulation of soil nitrogen based on nitrate-layered double hydroxide nanoparticle material, JOURNAL OF SOILS AND SEDIMENTS, 10.1007/s11368-013-0766-3, 14, 1, 60-66, 2014.01, Purpose Nitrate-layered double hydroxide material (nitrate-LDH) matrix can be considered as a potential formulation of delivering nitrogen into soil in a sustained manner.
Materials and methods The nitrate-LDH matrix was formulated by a co-precipitation technique and subsequently characterized by scanning electron microscopy, X-ray analysis, and infrared spectroscopy. The release of nitrate was monitored in different buffer mediums: buffer A as a simulated acidic soil solution and buffer B as a simulated neutral soil solution.
Results and discussion The stability of nitrate-LDH against thermal decomposition was evaluated by thermal gravimetric analysis. The nitrate-LDH supported a sustained controlled release process of nitrate during 16 days into acidic soil at 15 degrees C, while the release was continued to 20 days into neutral soil at the same temperature. The increase of soil temperature slightly enhanced the release of nitrate.
Conclusions We offered a potential management strategy of soil nitrogen leaching process. The nitrate form of layered double hydroxide material was used as a nitrogen fertilizer in order to monitor the release of nitrate anion into soil at different conditions..
93. Takeshi Mori, H. Tang, H. Kobayashi, Y. Niidome, Yoshiki Katayama, T. Niidome, CW/pulsed NIR irradiation of gold nanorods: Effect on transdermal protein delivery mediated by photothermal ablation, J. Controlled Release, 171, 178-183, 2013.10.
94. T. Hirano, A. Ono, H. Yamamoto, Y. Maeda, Takeshi Mori, M. Oshimura, K. Ute, Effect of composition and stereoregularity on phase-transition behavior of aqueous N-ethylacrylamide/N-n-propylacrylamide copolymer solutions, Polymer, 54, 56015608, 2013.10.
95. Satoshi Kushio, Akira Tsuchiya, Yuta Nakamura, Takanobu Nobori, Chan Woo Kim, Guo Xi Zhao, Taiki Funamoto, Eun Kyung Lee, Takuro Niidome, Takeshi Mori, Yoshiki Katayama, Cancer-specific gene carriers responding to cancer microenvironment: Acidosis and hyper-activated protein kinases, Biomedical Engineering - Applications, Basis and Communications, 10.4015/S101623721340005X, 25, 5, 2013.10, Protein kinase (PK)-responsive gene carriers modified with polyethylene glycol (PEG) chains using an acid-labile linker were developed. These carriers were obtained by modifying the PEG chains and substrate peptides for the PKs (PKA or PKCα) on the branched polyethyleneimine main chain. Polyplexes formed from these carriers and plasmid DNA (pDNA) were stably dispersed under neutral pH medium. The polyplexes were also taken up by cells on the release of the PEG chains under the slightly acidic extracellular pH associated with cancer cells. The polyplexes taken up by cells resulted in gene expression when the substrate peptides were phosphorylated by the intracellular PKs to release pDNA from the polyplexes. These novel gene carriers are expected to be promising for cancer-specific gene therapy via intravenous administration. © 2013 National Taiwan University..
96. C. W. Kim, R. Toita, J.-H. Kang, K. Li, E. K. Lee, G. X. Zhao, D. Funamoto, T. Nobori, Takeshi Mori, T. Niidome, Y. Nakamura, Yoshiki Katayama, Stabilization of Cancer-specific Gene Carrier via Hydrophobic Interaction for a Clear-cut Response to Cancer Signaling, J. Controlled Release, 170, 469-476, 2013.07.
97. J.-H. Kang, Takeshi Mori, H. Kitazaki, T. Niidome, Y. Nakanishi, K. Takayama, Yoshiki Katayama, Serum protein kinase Cα as a diagnostic biomarker of cancers, Cancer Biomarker, 13, 99-103, 2013.07.
98. H. Ikeda, J. Kamimoto, T. Yamamoto, A. Hata, Y. Otsubo, T. Niidome, M. Fukushima, Takeshi Mori, Yoshiki Katayama, A peptide microarray fabricated on a non-fouling phosphatidylcholine-polymer-coated surface for a high-fidelity analysis of a cellular kinome, Current Med. Chem., 20, 4419-25, 2013.06.
99. Y. Nakamura, C. W. Kim, A. Tsuchiya, S. Kushio, K. Li, T. Nobori, E. K. Lee, G. Xi Zhao, D. Funamoto, T. Niidome, Takeshi Mori, Yoshiki Katayama, Branched polyethylenimine-based PKCα-responsive gene carriers, J. Biomater. Sci.-Polym. Ed., 24, 1858-1868, 2013.06.
100. Takeshi Mori, S. Shiosaki, T. Nobori, R. Toita, Y. Nakamura, C. W. Kim, T. Yamamoto, T. Niidome, Yoshiki Katayama, A protein kinase assay based on FRET between quantum dots and fluorescently-labeled peptides, Chem. Commun., 49, 5592-5594, 2013.04.
101. J.-H. Kang, Takeshi Mori, H. Kitazaki, T. Niidome, K. Takayama, Y. Nakanishi, Yoshiki Katayama, Kinase Activity of Protein Kinase Calpha in Serum as a Diagnostic Biomarker of Human Lung Cancer, Anticancer, 33, 485-488, 2013.03.
102. J.-H. Kang, Takeshi Mori, H. Kitazaki, T. Niidome, K. Takayama, Y. Nakanishi, Yoshiki Katayama, Kinase Activity of Protein Kinase Calpha in Serum as a Diagnostic Biomarker of Human Lung Cancer, Anticancer, 33, 485-488, 2013.03.
103. K. Wakigawa, A. Gohda, S. Fukushima, Takeshi Mori, Yoshiki Katayama, Rapid and Selective determination of free chlorine in aqueous solution using electrophilic addition to styrene by gas chromatography/mass spectrometry, Talanta, 203, 81-85, 2013.02.
104. Y. Sakamura, M. Yoshiura, H. Tang, Takeshi Mori, Yoshiki Katayama, T. Niidome, Thermal enhancement of gene transfection in tumor cells mediated by the photothermal effect of gold nanorods, Chem. Lett., 42, 767-768, 2013.02.
105. M. R. Berber, I. H. Hafez, K. Minagawa, Takeshi Mori, M. Katoh, M. Tanaka, Uniform nanoparticles of hydrotalcite-like materials and their textural properties at optimized conditions of urea hydrothermal treatment, J Mol Struct, １０３３, １０４-１１２, 2013.01.
106. Masafumi Takeo, Takeshi Mori, Takuro Niidome, Shinichi Sawada, Kazunari Akiyoshi, Yoshiki Katayama, A polyion complex nanogel., Journal of colloid and interface science, 10.1016/j.jcis.2012.09.015, 390, 1, 78-84, 2013.01, Here, we synthesized dextrans modified with trivalent cationic or anionic groups. Aqueous solutions of the cationic and anionic dextrans were then mixed resulting in the formation of polyion complex nanogels (PIC-NGs), which have physically crosslinked salt bridges formed between the cationic and anionic groups. To prepare PIC-NGs in high yield, the content of ionic groups in the cationic and anionic dextrans should be low to avoid interparticle salt bridge formation. The structure of the PIC-NGs is easily affected by the ionic strength of the solution because of shielding of the charges in the ionic groups. However, the conversion of a small amount of the physical crosslinks to covalent crosslinks significantly improved the stability of the PIC-NGs. The covalent crosslinking also stabilized the PIC-NGs against pH change, which will destabilize the salt bridges. These results indicated that the conversion of the small amount of physical crosslinks to covalent crosslinks stabilized the other salt bridges..
107. Mohamed R. Berber, Inas H. Hafez, Keiji Minagawa, Masami Tanaka, Takeshi Mori, An efficient strategy of managing irrigation water based on formulating highly absorbent polymer-inorganic clay composites, JOURNAL OF HYDROLOGY, 10.1016/j.jhydrol.2012.08.051, 470, 193-200, 2012.11, The management of irrigation water presents a great challenge for the agriculture field. In view of increasing soil water-holding capacity and increasing water-use efficiency, an efficient strategy of managing irrigation water based on formulating highly absorbent polymer-inorganic clay composite (polyacrylic acid-layered double hydroxide: PAA-LDH) was offered. The PAA-LDH composite was synthesized by an incorporation/in situ polymerization technique. Scanning electron microscopy, X-ray analysis and infrared spectroscopy were used to confirm the composite structure. The thermal gravimetric analysis was applied to investigate the polymer thermal stability after the composite formation. The irrigation experiments were conducted in a wooden soil box with a transparent plexiglas side by using a subsurface drip irrigation system. The X-ray patterns and infrared spectra confirmed the incorporation of acrylic acid monomer (AA) into the gallery of LDH. The SEM images emphasized the composite structure of PAA-LDH and indicated its ability to absorb and keep water. The stability of PAA was promoted against the thermal decomposition after the composite formation. The composite structure of PAA-LDH worked as water barrier and secondary water source during the irrigation process. The soil moisture distribution patterns were enhanced after the application of PAA-LDH composites as a soil conditioner. (C) 2012 Elsevier B.V. All rights reserved..
108. Takeshi Mori, A colorimetric assay of protein kinase activity based on peptide-induced coagulation of gold nanorods, J. Collod. Interf. Sci. B: Biointerfaces, 99, 7, 2012.10.
109. H. Fukushima, Takuro Niidome, S. Yamashita, Takeshi Mori, Yoshiki Katayama, Yasuro Niidome, Controlled-Release System Mediated by a Retro Diels-Alder Reaction Induced by the Photothermal Effect of Gold Nanorods, Langmuir, 27, 14621, 2012.10.
110. Yasuyuki Akiyama, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, Conversion of rod-shaped gold nanoparticles to spherical forms and their effect on biodistribution in tumor-bearing mice., Nanoscale research letters, 10.1186/1556-276X-7-565, 7, 1, 565-565, 2012.10, Gold nanorods that have an absorption band in the near-infrared region and a photothermal effect have been used as nanodevices for near-infrared imaging and thermal therapy. Choice of the optimal shape of gold nanorods which relates optical properties and in vivo biodistribution is important for their applications. In the present study, to investigate the relationship between the shape of gold nanorods and their biodistribution after intravenous injection, we first prepared two types of gold nanorods that had distinct aspect ratios but had the same volume, zeta potential, and PEG density on the gold surface. Biodistributions of the two types of gold nanorods after intravenous injection into tumor-bearing mice were then compared. Although a slight difference in accumulation in the spleen was observed, no significant difference was observed in the liver, lung, kidney, and tumors. These results suggest that biodistribution of the gold nanorods in the aspect ratio range of 1.7 to 5.0, diameter of 10 to 50 nm, and volume of approximately 4 × 103 nm3 was dependent mainly on surface characteristics, PEG density, and zeta potential..
111. A. Hashidzume, A. Matsumoto, T. Mori, T. Shikata, T. Sato, Phase Behavior of Aqueous Solutions of Copolymers of N,N’-Diisopropylfumaramide and N-Isopropylacrylamide: Effect of the Density of Side Chains, Langmuir, 28, 5522, 2012.07.
112. Takeshi Mori, Yoshiki Katayama, Riki Toita, Gene carrier showing all-or-none response to cancer cell signaling, J. Am. Chem. Soc., 134, 15410-15417, 2012.07, In this work we designed a novel nano carrier, a linear polyethylenimine (LPEI)-peptide conjugate, for cancerspecific expression of transgenes. The conjugate was easily synthesized by using a click chemistry scheme orthogonal to the reactive side groups of the peptide, which is the substrate of protein kinase Cα (PKCα). Polyplexes of the conjugates with plasmid DNA (pDNA) were intact and stably dispersed even in the presence of cell lysate. Despite this stability, the polyplexes readily dissociated upon phosphorylation of the grafted peptides by PKCα. Because of its endosomal escape ability and adequate susceptibility to PKCα, the polyplexes
showed an all-or-none type response to PKCα activity in transgene expression in vitro. The polyplexes achieved cancer tissuespecific
transgene expression even for a tumor with a relatively low PKCα activity. Thus the LPEI−peptide conjugate has high potential as a nanocarrier for cancer-targeted gene therapy..
113. Takeshi Mori, Fluorometric detection of protein kinase Calpha activity based on phosphorylation-induced dissociation of a polyion complex, Anal. Biochem., 424, 130, 2012.05.
114. H. Tanaka, T. Mori, T. Niidome, Y. Katayama, Creating a unique environment for selecting reactive enzymes with DNA: ‘Sticky’ binding of oligocation-grafted polymers to DNA, Bioorg. Med. Chem., 20, 1346, 2012.04.
115. A. Tsuchiya, Y. Naritomi, S. Kushio, J.-H. Kang, M. Murata, M. Hashizume, T. Mori, T. Niidome, Y. Katayama, Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification, J. Biomed. Mater. Res. Part A, 100, 1136, 2012.04.
116. Takeshi Mori, Improvement in the colloidal stability of protein kinase-responsive polyplexes by PEG modification, J. Biomed. Mater. Res. Part A, 100, 1136-1141, 2012.04.
117. A Hashidzume, A. Matsumoto, T. Shikata, Takeshi Mori, T. Sato, Phase Behavior of Aqueous Solutions of Copolymers of N,N’-Diisopropylfumaramide and N-Isopropylacrylamide: Effect of the Density of Side Chains, Langmuir, 2012.04.
118. Takeshi Mori, Conversion of rod-shaped gold nanoparticles to spherical forms and their effect on biodistribution in tumor-bearing mice, Nanoscale Res. Lett., 7, 565, 2012.04.
119. Takeshi Mori, Sequential release of single-stranded DNAs from gold nanorods triggered by near-infrared light irradiation, Chem. Lett., 41, 711-712, 2012.04.
120. Keiji Minagawa, Mohamed R. Berber, Inas H. Hafez, Takeshi Mori, Masami Tanaka, Target delivery and controlled release of the chemopreventive drug sulindac by using an advanced layered double hydroxide nanomatrix formulation system, JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE, 10.1007/s10856-012-4566-x, 23, 4, 973-981, 2012.04, Target delivery and controlled release of the chemopreventive drug sulindac that possesses low water solubility present a great challenge for its pharmaceutical industry. Here, we offered an advanced nanomatrix formulation system of sulindac based on layered double hydroxide materials. The X-ray analysis and infrared spectroscopy confirmed the incorporation of sulindac into the gallery of the layered double hydroxides. The incorporation ratios of sulindac were recorded to be 45, 31 and 20 for coprecipitation, anion-exchange and reconstruction techniques, respectively. The scanning electron microscopy showed a nanomatrix-structure of similar to 50 nm. The release studies of sulindac-nanomatrix showed a 96% controlled release at the small intestine solution during 3 h(s), indicating an enhancement in the dissolution profile of sulindac after the matrix formation. The layered structure of the matrix supplied sulindac with a well-ordered structure and a relatively hydrophobic microenvironment that controlled the guest hydrolysis and reactivity during the release process. The laminar structure of layered double hydroxides offered a safe preservation for sulindac against photodecarboxylation, and enhanced the drug thermal stability from 190 to 230A degrees C. The ionic electrostatic interaction of sulindac through its acidic group with layered double hydroxides demolished the gastrointestinal ulceration..
121. R. Kurihara, D. Pissuwan, T. Mori, Y. Katayama, T. Niidome, Biodistribution and tumor localization of PEG-modified dendritic poly(L-lysine) oligonucleotide complexes, J. Biomater. Sci.-Polym. Ed., 23, 2369, 2012.02.
122. R. Kurihara, D. Pissuwan, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, Biodistribution and tumor localization of PEG-modified dendritic poly(L-lysine) oligonucleotide complexes, J. Biomater. Sci.-Polym. Ed., 23, 2369-2380, 2012.02.
123. Akira Tsuchiya, Daisuke Asai, Jeong-Hun Kang, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Correlation between phosphorylation ratios by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and radioactivities by radioactive assay., Analytical biochemistry, 10.1016/j.ab.2011.08.035, 421, 2, 773-5, 2012.02, To investigate the correlation between the counts per minute (CPM) by radioactivity assay and the phosphorylation ratio by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis, we prepared 136 peptide substrates. The correlation coefficient of phosphorylation ratios to CPM was 0.77 for all samples. However, the more the numbers of positively charged amino acids increased, the more the correlation coefficient increased. Although positively charged amino acids can have an effect on the correlation results, MALDI-TOF MS analysis is a useful means for monitoring phosphorylated peptide and protein kinase activity instead of radioactivity assays..
124. Akira Tsuchiya, Jeong-Hun Kang, Daisuke Asai, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Transgene regulation system responding to Rho associated coiled-coil kinase (ROCK) activation., Journal of controlled release : official journal of the Controlled Release Society, 10.1016/j.jconrel.2011.05.002, 155, 1, 40-6, 2011.10, Recently, we have proposed a new system of gene regulation called 'drug or gene delivery system responding to cellular signals' (D-RECS). In this system, transgene expression is activated in response to intracellular target protein kinases or proteases for safe, cell-specific gene delivery by using peptide-polymer conjugates. Here we applied this system to an intracellular Rho-associated coiled-coil kinase (ROCK) signal, which is activated abnormally in cardiovascular diseases. A ROCK responsive polymer consisting of neutral polymers in main chain and cationic ROCK substrate peptides in side chains was prepared and could form the complex with plasmid DNA. The complex was transferred into NIH3T3 cells with or without L-α-lysophosphatidic acid (LPA) that increases ROCK activity. At an N/P ratio of 2.0, a significant increase of the gene expression was identified in LPA-treated NIH3T3 cells, but was disappeared in NIH3T3 cells treated with ROCK specific inhibitor, Y-27632. These results suggest that the ROCK responsive polymer can regulate gene expression in response to ROCK activity..
125. Tetsuro Tomiyama, Riki Toita, Jeong-Hun Kang, Haruka Koga, Shujiro Shiosaki, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals., Nanoscale research letters, 10.1186/1556-276X-6-532, 6, 1, 532-532, 2011.09, We recently developed a novel tumor-targeted gene delivery system responding to hyperactivated intracellular signals. Polymeric carrier for gene delivery consists of hydrophilic neutral polymer as main chains and cationic peptide substrate for target enzyme as side chains, and was named polymer-peptide conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor-medicated endocytosis, into polymers mainly with a high cationic charge density such as polyethylenimine can increase tumor-targeted gene delivery. In the present study, we examined whether introduction of CS into PPC containing five cationic amino acids can increase gene expression in tumor cells. Size and zeta potential of plasmid DNA (pDNA)/PPC/CS complex were
126. Haruka Koga, Riki Toita, Takeshi Mori, Tetsuro Tomiyama, Jeong-Hun Kang, Takuro Niidome, Yoshiki Katayama, Fluorescent nanoparticles consisting of lipopeptides and fluorescein-modified polyanions for monitoring of protein kinase activity., Bioconjugate chemistry, 10.1021/bc200066w, 22, 8, 1526-34, 2011.08, Protein kinase (PK)-responsive nanoparticles (NPs) comprising a hydrophobically modified peptide substrate for PKs and a fluorescein-labeled polyanion (pA-F) were reported for monitoring PK activity via fluorescence intensity measurements. In this system, the formation of NPs by mixing lipopeptides and pA-Fs results in fluorescence quenching, while the quenched fluorescence recovered following dissociation of the NPs owing to the phosphorylation reaction of PKs. Eleven lipopeptides with different hydrophobic moieties (hydrocarbon and lithocholic acid) and four pA-Fs having main chains with differing flexibilities and fluorescein contents were synthesized and used to fabricate a series of twenty-four PK-responsive NP probes. The responses of the PK-responsive NP probes to PKs were evaluated to screen the most suitable NP probes. The assay system was then used to determine the IC(50) values for five inhibitors, the results of which were very similar to those previously reported. Thus, PK-responsive NPs are useful tools for high-throughput screening (HTS) of PK inhibitors..
127. Shujiro Shiosaki, Masanori Kuramoto, Riki Toita, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, A hydrophilic polymer grafted with a histone tail peptide as an artificial gene regulator., Bioorganic & medicinal chemistry, 10.1016/j.bmc.2011.05.011, 19, 13, 4101-5, 2011.07, In chromatin, gene transcription is regulated through posttranslational modifications on the histone N-terminal tail sequences, typically an acetyl group modification on lysine residues. To realize a simple model of the gene regulation of chromatin, we designed a hydrophilic polymer grafted with histone H3 tail peptides. The polyplex formed from the polymer and DNA suppressed the gene expression effectively although the polyplex was weaker than the polyplex of poly-L-lysine and DNA. This weaker polyplex afforded the acetylation of the lysine residue of the grafted peptides by histone acetyltransferase. Subsequently, the gene expression was activated due to the relaxation of the polyplex which was brought by a cationic charge decrease in the grafted peptides. This molecular system is the first functional model of the gene regulation of the chromatin..
128. Y. Asami, J. Oishi, H. Kitazaki, J. Kamimoto, J.-H. Kang, T. Niidome, T. Mori, Y. Katayama, A simple set-and-mix assay for screening of protein kinase inhibitors in cell lysates, Anal. Biochem., 418, 44-49 (2011)., Anal Biochem, 418, 44-49, 2011.06.
129. S. Shiosaki, M. Kuramoto, R. Toita, T. Mori, T. Niidome, Y. Katayama, A hydrophilic polymer grafted with a histone tail peptide represents an artificial gene regulator activated by a histone acetyltransferase, Bioorg. Med. Chem., 19, 4101-41405 (2011)., Bioorg Med Chem, 19, 4101-41405, 2011.05.
130. Shuji Yamashita, Hiromitsu Fukushima, Yasuyuki Akiyama, Yasuro Niidome, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, Controlled-release system of single-stranded DNA triggered by the photothermal effect of gold nanorods and its in vivo application, BIOORGANIC & MEDICINAL CHEMISTRY, 10.1016/j.bmc.2011.02.042, 19, 7, 2130-2135, 2011.04, Gold nanorods have strong absorption bands in the near-infrared region, in which light penetrates deeply into tissues. The absorbed light energy is converted into heat by gold nanorods, the so-called 'photothermal effect'. Hence, gold nanorods are expected to act not only as on-demand thermal converters for photothermal therapy but also as controllers of a drug-release system responding to irradiation by near-infrared light. To achieve a controlled-release system that can be triggered by light irradiation, double-stranded DNA (dsDNA) was modified on gold nanorods. When the dsDNA-modified gold nanorods were irradiated by near-infrared light, the single-stranded DNA (ssDNA) was released from gold nanorods due to the photothermal effect. The amount of released ssDNA was dependent upon the power and exposure time of light irradiation. Release of ssDNA was also observed in tumors grown on mice after light irradiation. Such a controlled-release system of oligonucleotide triggered by the photothermal effect could expand the applications of gold nanorods that have unique optical characteristics in medicinal fields. (C) 2011 Elsevier Ltd. All rights reserved..
131. Oligonuleotide delivery with dendritic poly(L-lysine) for treatments of the liver disorders
A cationic peptide dendrier, dendritic poly(L-lysine), forms complexes with oligonucleotides and can deliver them to liver after intravenous injection. Here, we tried to deliver apolipoprotein B-specific siRNA for the treatment of hypercholesterolemia and NFκB decoy for the hepatitis treatment. Significant therapeutic effects in those disease model mice were observed after intravenous injection of the oligonucleotides complexes with dendritic poly(L-lysine). © 2010 Materials Research Society..
132. Atsushi Shiotani, Yasuyuki Akiyama, Takahito Kawano, Yasuro Niidome, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, Active accumulation of gold nanorods in tumor in response to near-infrared laser irradiation., Bioconjugate chemistry, 10.1021/bc100284s, 21, 11, 2049-54, 2010.11, Gold nanorods, rod-shaped gold nanoparticles, have strong absorbance in the near-infrared region, and the absorbed light energy can be converted to heat, the so-called photothermal effect. The gold nanorods were coated with thermoresponsive polymers, which have different phase transition temperatures that were controlled by adding comonomers, N,N-dimethylacrylamide (DMAA) or acrylamide (AAm) to N-isopropylacrylamide (NIPAM). The phase transition temperatures of poly(NIPAM-DMAA) and poly(NIPAM-AAm)-coated gold nanorods were 38 and 41 °C, respectively, while polyNIPAM-coated gold nanorods showed phase transition at 34 °C. Irradiation of the coated gold nanorods using the near-infrared laser induced a decrease in their sizes due to a phase transition of the polymer layers. Poly(NIPAM-AAm)-coated gold nanorods stably circulated in the blood flow without a phase transition after intravenous injection. Irradiation of near-infrared light at a tumor after the injection resulted in the gold specifically accumulating in the tumor. This novel accumulation technique which combines a thermoresponsive polymer and the photothermal effect of the gold nanorods should be a powerful tool for targeted delivery in response to light irradiation..
133. Mohamed R. Berber, Inas H. Hafez, Keiji Minagawa, Takeshi Mori, Masami Tanaka, Nanocomposite Formulation System of Lipid-Regulating Drugs Based on Layered Double Hydroxide: Synthesis, Characterization and Drug Release Properties, PHARMACEUTICAL RESEARCH, 10.1007/s11095-010-0175-x, 27, 11, 2394-2401, 2010.11, To design a nanocomposite formulation system of lipid-regulating drugs with versatile approaches using layered double hydroxide (LDH) material.
The co-precipitation technique has been used to prepare the selected drugs [bezafibrate (BZF) and clofibric acid (CF)]-LDH nanocomposites. The nanocomposite materials (BZF-LDH and CF-LDH) were characterized by X-ray powder diffraction, infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The in vitro study was investigated in simulated gastrointestinal solutions at 36.8A degrees C.
X-ray measurement and spectroscopic analysis indicated the formation of fully monophase drug-nanocomposites. The nanocomposites' gallery heights were calculated to be 23.5 and 16.3 for BZF and CF, respectively. The new gallery heights indicated that BZF and CF drugs have been stacked into LDH as a monolayer with a staggered inter-digitated arrangement. The size of the nanocomposites described by SEM microscopy was similar to aEuro parts per thousand 0.1 mu m. The nanocomposite formulation has improved the drugs properties (thermal stability, dissolution, and controlled release) beside the achievement of drug target delivery.
Nanocomposites composed of lipid-regulating drugs (BZF and CF) with LDH were successfully synthesized as a new formulation system of this drug category. The LDH nanocomposite formulation system has improved the drugs release properties..
134. Xiaoming Han, Tatsuhiko Sonoda, Takeshi Mori, Go Yamanouchi, Takayuki Yamaji, Syuhei Shigaki, Takuro Niidome, Yoshiki Katayama, Protein kinase substrate profiling with a high-density peptide microarray., Combinatorial chemistry & high throughput screening, 13, 9, 777-89, 2010.11, We describe a powerful peptide microarray for profiling protein kinase substrates that combines the merits of chemoselective immobilization of peptides to achieve high density spots with the advantages of fluorescence-based analysis of phosphorylation for nonhazardous detection. For detection of on-chip phosphorylation, we used a fluorescence-labeled antiphosphotyrosine antibody to detect phosphotyrosine and a biotinylated Phostag, which was subsequently bound with a fluorescence-labeled streptavidin for phosphoserine/threonine. More than 290 kinds of Tyr peptides and over 1,100 kinds of Ser/Thr peptides were chemoselectively immobilized onto a glass surface in a high-density format to profile a panel of protein kinases, including c-Src, c-Abl, EGFR, JNK1, ERK2, p38α, and PKA. Many novel, highly reactive and specific peptides were identified as substrates for each protein kinase. Most substrates had the consensus motifs that have been reported previously but some new motifs were also found. The identification of two designed peptides that have higher reactivity than the famous PKA substrate (Kemptide) indicates that analysis of the amino acid biases of substrates is very helpful to the design of new substrates with high reactivity. Thus, the high-density peptide microarray is expected to be a powerful approach for high-throughput discovery of potential substrates for protein kinases..
135. Takuro Niidome, Atsushi Shiotani, Takeshi Mori, Yoshiki Katayama, Targeted delivery of gold nanorods modified with thermo-sensitive polymer., Journal of controlled release : official journal of the Controlled Release Society, 10.1016/j.jconrel.2010.07.027, 148, 1, e65-6-6, 2010.11.
136. Tetsuro Tomiyama, Riki Toita, Jeong-Hun Kang, Daisuke Asai, Shujiro Shiosaki, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Tumor therapy by gene regulation system responding to cellular signal., Journal of controlled release : official journal of the Controlled Release Society, 10.1016/j.jconrel.2010.08.017, 148, 1, 101-105, 2010.11, For safe and efficient gene therapy, the development of gene delivery systems to specifically target tumor cells is one of the most important issues regarding present gene delivery methodologies. Recently, we have developed a novel drug or gene delivery system responding to cellular signals (D-RECS) that can activate transgenes in response to hyperactivated cellular signals. Especially, a protein kinase C (PKC)α-responsive polymeric carrier (polymer-peptide conjugate, PPC(S)) showed highly specific gene expression to tumor cells and tissues. In the present study, we have applied the PKCα-responsive polymeric carrier to tumor gene therapy. PPC(S) consists of a polyacrylamide backbone and cationic peptide side chains, which together make PPC(S) as a positive polymer, a PKCα-specific substrate. A negative control polymer, PPC(A), was also prepared by replacing a serine residue at the phosphorylation site of the peptide side chains of PPC(S) with alanine. A complex of PPC(S) with caspase-8 or the herpes simplex virus-thymidine kinase (HSV-TK) gene as therapeutic genes was transfected into certain tumor cells or tissues. The prodrug ganciclovir (GCV) was then intraperitoneally injected into PPC(S)/HSV-TK complex-transfected mice. The PPC(S)/gene complex showed significant cytotoxicity toward the tumor cells and suppression of tumor growth, compared with those of the PPC(A)/gene complex or PBS. These results indicate that the PKCα-responsive polymeric carrier is applicable for tumor-targeted gene therapy..
137. High-throughput detection of protein kinase activities in cell lysate based on the aggregation of gold nanoparticles with peptides
Cationic peptides were used as coagulant of gold nano-particle (GNP, 20 nm) for the monitoring cellular protein kinase activities. If cationic peptides, which are designed as specific substrates to target protein kinases, were added into the GNP dispersion, the color of the dispersion changed from red to blue due to the aggregation. On the other hand, if the peptide was phosphorylated with target protein kinase, addition of the phosphorylated peptide didn't change the color of the GNP dispersion. Thus, this system can be a rapid assay of protein kinase activity. The method was applicable to the assay of intracellular protein kinase by using cell lysate. In addition, we applied the system for high-throughput screening of protein kinase inhibitor using 1300 kinds of chemical library. The result indicated that the method was also useful for the drug discovery. © 2010 Materials Research Society..
138. Inas H. Hafez, Mohamed R. Berber, Keiji Minagawa, Takeshi Mori, Masami Tanaka, Design of a Multifunctional Nanohybrid System of the Phytohormone Gibberellic Acid Using an Inorganic Layered Double-Hydroxide Material, JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 10.1021/jf102501n, 58, 18, 10118-10123, 2010.09, To offer a multifunctional and applicable system of the high-value biotechnological phytohormone gibberellic acid (GA), a nanohybrid system of GA using the inorganic Mg-Al layered double-hydroxide material (LDH) was formulated. The ion-exchange technique of LDH was applied to synthesize the GA-LDH hybrid. The hybrid structure of GA LDH was confirmed by different spectroscopic techniques. The nanohybrid size was described by SEM to be similar to 0.1 mu m. The GA-LDH nanohybrid structure was the key parameter that controlled GA properties. The layered molecular structure of LDH limited the interaction of GA molecules in two-dimensional directions. Accordingly, GA molecules did not crystallize and were released in an amorphous form suitable for dissolution. At various simulated soil solutions, the nanohybrids showed a sustained release process following Higuchi kinetics. The biodegradation process of the intercalated GA showed an extended period of soil preservation as well as a slow rate of degradation..
139. Jun Oishi, Joohee Jung, Akira Tsuchiya, Riki Toita, Jeong-Hun Kang, Takeshi Mori, Takuro Niidome, Katsuyuki Tanizawa, Shun'ichi Kuroda, Yoshiki Katayama, A gene-delivery system specific for hepatoma cells and an intracellular kinase signal based on human liver-specific bionanocapsules and signal-responsive artificial polymer., International journal of pharmaceutics, 10.1016/j.ijpharm.2010.06.012, 396, 1-2, 174-8, 2010.08, Recently, our group has proposed a novel gene-regulation system responding to cAMP-dependent protein kinase (PKA) that has been applied to living cells. In this study, human liver-specific bionanocapsules (BNCs) are used as a gene-delivery system to increase transfection efficiency and to target specific cell types. BNCs can efficiently deliver a target gene to human hepatocytes and hepatoma cells in vitro or in vivo. The combination of a signal-responsive gene-delivery system with BNCs led to an increase in the transfection efficiency and selectivity for hepatoma cells. Expression from the delivered gene was identified from PKA-activated hepatoma cells (HepG2), but not from colon tumor cells (WiDr). These results show that the combination of a gene-regulation system responding to an intracellular signal with BNC can be used for the selective treatment of human hepatoma cells..
140. Jeong-Hun Kang, Jun Oishi, Jong-Hwan Kim, Moeko Ijuin, Riki Toita, Byungdug Jun, Daisuke Asai, Takeshi Mori, Takuro Niidome, Katsuyuki Tanizawa, Shun'ichi Kuroda, Yoshiki Katayama, Hepatoma-targeted gene delivery using a tumor cell-specific gene regulation system combined with a human liver cell-specific bionanocapsule., Nanomedicine : nanotechnology, biology, and medicine, 10.1016/j.nano.2010.01.007, 6, 4, 583-9, 2010.08, Hepatoma (hepatocellular carcinoma) is the most common type of malignant tumor originating in the liver and has a relatively low 5-year survival rate. The development of hepatoma-targeted therapy is needed to increase treatment efficiency and to reduce the incidence of undesirable side effects. In this study we developed a novel hepatoma-targeted gene delivery system. The gene delivery system was prepared by combining a human liver cell-specific bionanocapsule (BNC) and a tumor cell-specific gene regulation polymer, which responds to hyperactivated protein kinase C alpha in hepatoma cells. The complex of the polymer-DNA with BNCs was delivered into cells and tissues. The developed system showed increased transfection efficiency and resulted in cell-specific gene expression in hepatoma cells and tissues (HuH-7), but no gene expression in normal human hepatocytes or human epidermoid tumor cells (A431). The combination of a tumor cell-specific gene regulation system responding to protein kinase C alpha and BNCs showed excellent potential for the selective treatment of hepatomas. The system could be a useful method with applications in hepatoma-specific gene therapy and molecular imaging. From the clinical editor: Hepatocellular carcinoma is the most common type of malignant tumor in the liver with a low 5-year survival rate. In this study, a novel hepatoma-targeted gene delivery system was prepared by combining a human liver cell-specific bionanocapsule and a tumor cell-specific gene regulation polymer, which responds to hyperactivated protein kinase C (PKC)a in hepatoma cells. The system could be a useful in hepatoma-specific gene therapy and molecular imaging..
141. Takuro Niidome, Akira Ohga, Yasuyuki Akiyama, Kazuto Watanabe, Yasuro Niidome, Takeshi Mori, Yoshiki Katayama, Controlled release of PEG chain from gold nanorods: targeted delivery to tumor., Bioorganic & medicinal chemistry, 10.1016/j.bmc.2010.04.070, 18, 12, 4453-8, 2010.06, Gold nanorods exhibit strong absorbance of light in the near infrared region, which penetrates deeply into tissues. Since the absorbed light energy is converted into heat, gold nanorods are expected to act as a contrast agent for in vivo bioimaging and as a thermal converter for photothermal therapy. To construct a gold nanorod targeted delivery system for tumor a peptide substrate for urokinase-type plasminogen activator (uPA), expressed specifically on malignant tumors, was inserted between the PEG chain and the surface of the gold nanorods. In other words, we constructed PEG-peptide-modified gold nanorods. After mixing the gold nanorods with uPA, the PEG chain was released from the surface of the gold and subsequently nanorod aggregation took place. The formation of the aggregation was monitored as a decrease in light absorption at 900 nm. Tumor homogenate induced a significant decrease in this absorption. Larger amount of the PEG-peptide-modified gold nanorods bound to cells expressing uPA in vitro compared with control gold nanorods, which had scrambled sequence of the peptide. The PEG-peptide-modified gold nanorods showed higher accumulation in tumor than the control after they were injected intravenously into tumor-bearing mice, however, the density of the peptide on the surface of the gold nanorods was a key factor of their biodistributions. This targeted delivery system, which responds to uPA activity, is expected to be a powerful tool for tumor bioimaging and photothermal tumor therapy..
142. Takeshi Mori, Suguru Beppu, Mohamed R Berber, Hironori Mori, Takumi Makimura, Ayako Tsukamoto, Keiji Minagawa, Tomohiro Hirano, Masami Tanaka, Takuro Niidome, Yoshiki Katayama, Tatsuya Hirano, Yasushi Maeda, Design of temperature-responsive polymers with enhanced hysteresis: alpha,alpha-disubstituted vinyl polymers., Langmuir : the ACS journal of surfaces and colloids, 10.1021/la100020t, 26, 12, 9224-32, 2010.06, Three temperature-responsive polymers which are alpha,alpha-disubstituted vinyl polymers having two amphiphilic groups (ethylamide or ethylester) per monomeric unit were designed. Two of these polymers showed unusually large hysteresis in their phase transition temperatures between a heating and a cooling process. This hysteresis resulted from the extremely slow kinetics of the dissolution process of the aggregated polymer chains in the cooling process due to intra- and interchain interactions including hydrogen bonding and hydrophobic interaction. The high density of the amphiphilic substituents on the polymer chain due to the alpha,alpha-disubstituted structure enhanced these intra- and interchain interactions. The large hysteresis was also observed in the volume change of a corresponding hydrogel. These new classes of temperature-responsive polymers are interesting materials because their large hystereses can be regarded as erasable memory function..
143. Mohamed R. Berber, Hironori Mori, Inas H. Hafez, Keiji Minagawa, Masami Tanaka, Takuro Niidome, Yoshiki Katayama, Atsushi Maruyama, Tomohiro Hirano, Yasushi Maeda, Takeshi Mori, Unusually Large Hysteresis of Temperature-Responsive Poly(N-ethyl-2-propionamidoacrylamide) Studied by Microcalorimetry and FT-IR, JOURNAL OF PHYSICAL CHEMISTRY B, 10.1021/jp102681q, 114, 23, 7784-7790, 2010.06, We reported here the full characterization of the hysteresis of the phase transition behavior of an aqueous solution of poly(N-ethyl-2-propionamidoacrylamide) (PNEPA), which has a unique alpha,alpha-disubstituted structure, by using microcalorimetry and FT-IR. Phase transition temperatures near the thermodynamic equilibrium were determined by extrapolating the scanning rate of the microcalorimetry to zero. The calculated hysteresis from the phase transition temperature was unusually very large (similar to 8 degrees C). FT-IR analysis indicated that the large hysteresis of PNEPA resulted from a coupling of intra-/intermonomeric unit hydrogen bonds, which is known to occur in a beta-sheet of proteins but has never been reported in temperature-responsive polymers. The effects of the molecular weight and polymer concentration on the hysteresis were studied by using fractionated PNEPAs and it was found that a low molecular weight and a low concentration enhanced the hysteresis..
144. Jeong-Hun Kang, Yoji Asami, Masaharu Murata, Hirotaro Kitazaki, Noriaki Sadanaga, Eriko Tokunaga, Satoko Shiotani, Satoko Okada, Yoshihiko Maehara, Takuro Niidome, Makoto Hashizume, Takeshi Mori, Yoshiki Katayama, Gold nanoparticle-based colorimetric assay for cancer diagnosis., Biosensors & bioelectronics, 10.1016/j.bios.2009.12.022, 25, 8, 1869-74, 2010.04, A novel gold nanoparticle (GNP)-based colorimetric assay was developed for cancer diagnosis. This system is based on the noncrosslinking aggregation mechanism with a cationic protein kinase C (PKC) alpha-specific peptide substrate, which is used as a coagulant of citrate-coated GNP with anionic surface charges. The phosphorylation of peptide substrates by PKCalpha suppressed GNP aggregation, resulting in a red color, but in the case of non-phosphorylation, the color of the GNP solution changed from red to blue, indicating particle aggregation. Moreover, a correlation between the color change of the GNP dispersions and the level of activated PKCalpha was identified from experiments using cancer cell lines, or xenografted mouse cancer and normal mouse tissues. When our system was applied to human breast cancers and normal human breast tissues, cancer tissue lysates became red in color, indicating GNP dispersion, while all lysates from normal tissue turned the GNP solution blue. MALDI-TOF MS analysis and Western blotting experiment confirmed that these different results between cancer and normal tissues reflected the difference in PKCalpha activity. This study is the first report on the application of the GNP-based colorimetric assay to the diagnosis of cancer..
145. Daisuke Asai, Masanori Kuramoto, Yoko Shoji, Jeong-Hun Kang, Kota Bae Kodama, Kenji Kawamura, Takeshi Mori, Hiroshi Miyoshi, Takuro Niidome, Hideki Nakashima, Yoshiki Katayama, Specific transgene expression in HIV-infected cells using protease-cleavable transcription regulator., Journal of controlled release : official journal of the Controlled Release Society, 10.1016/j.jconrel.2009.08.025, 141, 1, 52-61, 2010.01, Gene therapy is a promising strategy for the treatment of HIV infection, but cell specificity remains an issue. Recently we have developed a new concept for a drug or gene delivery system responding to cellular signals (D-RECS) to achieve cell-specific transgene expression using a non-viral polymer-based vehicle. According to this concept, intracellular signaling enzymes, which are activated specifically in target cells, are used to trigger transgene expression. We previously applied this concept to HIV-1 protease and showed that the recombinant protease could act as a suitable signal. Here we further developed this system to achieve highly specific transgene expression in HIV-infected cells. We prepared a polymeric gene regulator grafted with a cationic peptide containing the HIV-Tat peptide via a specific substrate for HIV-1 protease. The regulator formed a stable polyplex with the transgene, suppressing its transcription. HIV-1 protease cleaved the peptide and released the transgene, which was consequently expressed specifically in activated HIV-infected cells, but remained unreleased and inactive in uninfected cells. The validity of this approach was further confirmed by applying it to the CVB1 2A protease of coxsackievirus (Picornaviridae family). This strategy should be widely applicable for specific expression of a variety of therapeutic genes in virus-infected cells..
146. Takuro Niidome, Yusuke Sugao, Kazuto Watanabe, Takeshi Mori, Yoshiki Katayama, DECOY DELIVERY INTO LIVER USING DENDRITIC POLY(L-LYSINE), JOURNAL OF GENE MEDICINE, 11, 12, 1165-1165, 2009.12.
147. Jeong-Hun Kang, Riki Toita, Tetsuro Tomiyama, Jun Oishi, Daisuke Asai, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Cellular signal-specific peptide substrate is essential for the gene delivery system responding to cellular signals., Bioorganic & medicinal chemistry letters, 10.1016/j.bmcl.2009.09.034, 19, 21, 6082-6, 2009.11, Recently, there is a growing interest in the intracellular signal-targeting gene therapy or diagnosis, mainly by using the reaction of targeting enzymes with peptide substrates. In the present study, we proved the importance of target intracellular signal-specificity peptide substrate for intracellular signals-targeting gene therapy or diagnosis. Protein kinase C (PKC) was used as a trigger to activate the transgene expression. Two peptides, a positive peptide showing phosphorylation levels on several PKC isozymes (PKCalpha, betaII, gamma, epsilon, eta, zeta, and iota/lambda) and a negative peptide in which the phosphorylation site was destroyed by changing from serine to alanine, were designed. Moreover, two polymers possessing each peptide as a pendant chain, a PKC-responsive conjugate [PPC(S)] and a negative control conjugate [PPC(A)], were synthesized. After the introduction of complexes into cells or tissues, gene expression for PPC(S)/DNA complexes was higher that for PPC(A)/DNA complexes. However, no difference in gene expression between B16 melanoma tumors and normal skin tissues was identified. These results suggest that a peptide substrate specific to a target intracellular signal is very important for intracellular signals-targeting gene therapy or diagnosis..
148. J.-H. Kang, D. Asai, J.-H. Kim, T. Mori, R. Toita, T. Tomiyama, Y. Asami, J. Oishi, Y. T. Sato, T. Niidome, B. Jun, H. Nakashima, Y. Katayama, Design of polymeric carriers for cancer-specific gene targeting: Utilization of abnormal protein kinase Cα activation in cancer cells, J. Am. Chem. Soc, 130, 14906-14907, 2009.10.
149. Riki Toita, Jeong-Hun Kang, Jong-Hwan Kim, Tetsuro Tomiyama, Takeshi Mori, Takuro Niidome, Byungdug Jun, Yoshiki Katayama, Protein kinase C alpha-specific peptide substrate graft-type copolymer for cancer cell-specific gene regulation systems., Journal of controlled release : official journal of the Controlled Release Society, 10.1016/j.jconrel.2009.06.011, 139, 2, 133-9, 2009.10, We recently proposed a novel gene regulation system responding to specifically and abnormally activated intracellular enzymes in diseased cells. In the present study, we focused on protein kinase C (PKC)alpha, which is hyper-activated in most tumor cells, as a trigger for transgene regulation. We prepared cationic copolymers comprising hydrophilic and neutral polymers in main chains and cationic peptide substrates with different contents in side chains. Our copolymer with high peptide content (>3 mol%) condensed with pDNA more weakly than with poly(L-lysine) (pLL) having a similar molecular weight, but gene suppression was nearly identical to that of pLL, probably due to the steric hindrance of the main chains in our copolymer. Steric hindrance of the main chains barely affected the phosphorylation reaction of the pendant peptide. In cell and mouse experiments, higher gene expression was observed in complexes of pDNA with copolymers pended PKC alpha-specific substrate peptide than that in complexes with negative copolymers pended peptide substituted phosphorylation site of serine residues with alanine. These results indicate that our system can recognize intracellular PKC alpha as a trigger to regulate transgene expression, and may be useful for tumor gene therapy..
150. Yasuyuki Akiyama, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, The effects of PEG grafting level and injection dose on gold nanorod biodistribution in the tumor-bearing mice., Journal of controlled release : official journal of the Controlled Release Society, 10.1016/j.jconrel.2009.06.006, 139, 1, 81-4, 2009.10, Gold nanorods have strong absorbance in the near infrared region, which penetrates deeply into tissues, where the absorbed light energy is converted into heat. Therefore, gold nanorods are expected to act as an effective contrast agent for in vivo bioimaging and as a thermal converter for photothermal therapy. We grafted various amounts of polyethylene glycol (PEG) onto the surface of gold nanorods and investigated the effects of grafting level and injection dose on the biodistribution in the tumor-bearing mice after intravenous injection and enhanced permeability and retention (EPR). Higher PEG grafting levels were advantageous for reticuloendothelial system (RES) avoidance and for suppression of aggregation of the gold nanorods in the circulation. Modification with a PEG:gold molar ratio of 1.5 was sufficient to show both prolonged circulation and the EPR effect. When the injection dose was increased above 19.5 microg of gold, the RES uptake in the liver was saturated and surplus gold nanorods were distributed to other tissues, especially the spleen and the tumor. The results of this study will provide an important basis for the development of cancer therapies mediated by the photothermal effect of gold nanorods..
151. Kazuki Inamori, Motoki Kyo, Kazuki Matsukawa, Yusuke Inoue, Tatsuhiko Sonoda, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Establishment of screening system toward discovery of kinase inhibitors using label-free on-chip phosphorylation assays., Bio Systems, 10.1016/j.biosystems.2009.04.007, 97, 3, 179-85, 2009.09, We describe a label-free method for the kinase inhibition assay toward discovery of kinase inhibitors. The surface plasmon resonance (SPR) imaging analysis using zinc(II) compound was adopted on the on-chip phosphorylation analysis. In this study, following three subjects were focused: (1) to monitor the inhibition of three inhibitors supporting by their specific inhibition mechanisms, (2) to quantify the inhibitory activities, and (3) to prove the reliability of the obtained 50% inhibition concentration (IC(50)) value. First, the inhibitory activities of Amide 5-24, H-89 and Gö6983 on PKA and PKCdelta were determined, and specific inhibitions for two kinases could be observed quantitatively. Second, the inhibition curves of Amide 5-24, Amide 14-22 and H-89 were obtained, and the results supported the two previous reports: (1) the inhibition efficiency of Amide 5-24 was much higher than that of Amide 14-22, and (2) the inhibitory activity of H-89 followed ATP-binding site blocking mechanism. Last, the obtained IC(50) values by the SPR imaging were almost corresponded to those by the solution assay, although on-chip phosphorylation efficiency was low (approximately 12%). In conclusion, validation of the on-chip phosphorylation analysis for kinase inhibitors was achieved. This label-free method might be applied for discovery of kinase inhibitors..
152. Daisuke Asai, Akira Tsuchiya, Jeong-Hun Kang, Kenji Kawamura, Jun Oishi, Takeshi Mori, Takuro Niidome, Yoko Shoji, Hideki Nakashima, Yoshiki Katayama, Inflammatory cell-specific transgene expression system responding to Ikappa-B kinase beta activation., The journal of gene medicine, 10.1002/jgm.1342, 11, 7, 624-32, 2009.07, BACKGROUND: Control of inflammation is essential for the clinical management of many common human diseases. However, there are few generally applicable strategies to convert an abnormal intracellular signal into a gene expression that leads to normalization of the intracellular environment. Recently, we proposed a novel strategy termed D-RECS (i.e. drug or gene delivery system responding to cellular signals) to convert an intracellular signal to transgene expression. In the present study, we applied this concept to inflammatory cells using Ikappa-B kinase as a signal molecule that triggers the gene expression. METHODS: Candidate cationic substrates of Ikappa-B kinase (IKK)beta were synthesized and their reactivity was investigated. Then, polymers grafted with these peptides were prepared by radical polymerization. Polymer/DNA complexes (polyplexes) were prepared by mixing plasmid DNAs with the polymers. The behaviour of these polyplexes by adding IKKbeta was examined. Furthermore, changes of gene expression were evaluated after the microinjection of polyplex into living cells under conditions of nuclear factor (NF)-kappaB activation. RESULTS: Synthetic peptides with additional lysine residues were well phosphorylated by IKKbeta. Both the polymer and the polyplex were also phosphorylated by IKKbeta. The results of gel shift assay showed that the polyplex was disintegrated and free DNA was released in the presence of IKKbeta. The polyplex comprising-green fluorescent protein plasmid DNA and the polymer expressed the transgene in living cells exposed to a pro-inflammatory stimulus. CONCLUSIONS: Our concept of cell-specific gene expression was demonstrated to work in inflammatory cells. This method may provide a unique strategy for gene therapy exclusively in inflammatory cells..
153. K. Watanabe, M. Harada-Shiba, A. Suzuki, R. Gokuden, R. Kurihara, Y. Sugao, T. Mori, Y. Katayama, T. Niidome, In vivo siRNA delivery with dendritic poly(L-lysine) for the treatment of hypercholesterolemia, Molecular BioSystems, 5, 1306-1310, 2009.06.
154. K. Watanabe, M. Harada-Shiba, A. Suzuki, R. Gokuden, R. Kurihara, Y. Sugao, T. Mori, Y. Katayama, T. Niidome, In vivo siRNA delivery with dendritic poly(L-lysine) for the treatment of hypercholesterolemia, Molecular BioSystems, 5, 1306-1310, 2009.06.
155. K. Watanabe, M. Harada-Shiba, A. Suzuki, R. Gokuden, R. Kurihara, Y. Sugao, T. Mori, Y. Katayama, T. Niidome, In vivo siRNA delivery with dendritic poly(L-lysine) for the treatment of hypercholesterolemia, Molecular BioSystems, 5, 1306-1310, 2009.06.
156. Kentaro Sao, Masaharu Murata, Yuri Fujisaki, Kaori Umezaki, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Makoto Hashizume, A novel protease activity assay using a protease-responsive chaperone protein., Biochemical and biophysical research communications, 10.1016/j.bbrc.2009.03.129, 383, 3, 293-7, 2009.06, Protease activity assays are important for elucidating protease function and for developing new therapeutic agents. In this study, a novel turbidimetric method for determining the protease activity using a protease-responsive chaperone protein is described. For this purpose, a recombinant small heat-shock protein (sHSP) with an introduced Factor Xa protease recognition site was synthesized in bacteria. This recombinant mutant, FXa-HSP, exhibited chaperone-like activity at high temperatures in cell lysates. However, the chaperone-like activity of FXa-HSP decreased dramatically following treatment with Factor Xa. Protein precipitation was subsequently observed in the cell lysates. The reaction was Factor Xa concentration-dependent and was quantitatively suppressed by a specific inhibitor for Factor Xa. Protein aggregation was detected by a simple method based on turbidimetry. The results clearly demonstrate that this assay is an effective, easy-to-use method for determining protease activities without the requirement of labeling procedures and the use of radioisotopes..
157. Tomohiro Hirano, Takahiro Kamikubo, Yuya Okumura, Yoichi Bando, Ryosuke Yamaoka, Takeshi Mori, Koichi Ute, Heterotactic-Specific Radical Polymerization of N-isopropylacrylamide and Phase Transition Behavior of Aqueous Solution of Heterotactic Poly(N-isopropylacrylamide), JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 10.1002/pola.23338, 47, 10, 2539-2550, 2009.05, Radical polymerization of N-isopropylacrylamide (NIPAAm) in toluene at low temperatures, in the presence of fluorinated-alcohols, produced heterotactic polymer comprising an alternating sequence of meso and racemo dyads. The heterotacticity reached 70% in triads when polymerization was carried out at -40 degrees C using nonafluoro-tert-butanol as the added alcohol. NMR analysis revealed that formation of a 1:1 complex of NIPAAm and fluorinated-alcohol through C=O center dot center dot center dot H-O hydrogen bonding induces the heterotactic specificity. A mechanism for the heterotactic-specific polymerization is proposed. Examination of the phase transition behavior of aqueous solutions of heterotactic poly(NIPAAm) revealed that the hysteresis of the phase transition between the heating and cooling cycles depended on the average length of meso dyads in poly(NIPAAm). (C) 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2539-2550, 2009.
158. Takeshi Mori, Go Yamanouchi, Xiaoming Han, Yusuke Inoue, Syuhei Shigaki, Takayuki Yamaji, Tatsuhiko Sonoda, Kei Yasui, Hisato Hayashi, Takuro Niidome, Yoshiki Katayama, Signal-to-noise ratio improvement of peptide microarrays by using hyperbranched-polymer materials, JOURNAL OF APPLIED PHYSICS, 10.1063/1.3116124, 105, 10, 102020, 2009.05, The fabrication of peptide microarrays using hyperbranched polymers (HBPs) to improve the signal-to-noise ratio was demonstrated. Due to a high density of reactive groups at the chain ends of the HBPs, as well as to their spherical shape, HBPs can be used as linkers to increase the amount of immobilized peptides through raising the specific surface area of the glass substrate. A zwitterionic HBP was used as a blocking agent to reduce the noise level of the peptide microarrays. The zwitterionic HBP shows comparably excellent blocking ability to a commercially available BSA-based blocking agent. Thus, it was concluded that HBPs have high potential for the fabrication of highly sensitive peptide microarrays..
159. Xiaoming Han, Go Yamanouchi, Takeshi Mori, Jeong-Hun Kang, Takuro Niidome, Yoshiki Katayama, Monitoring protein kinase activity in cell lysates using a high-density peptide microarray., Journal of biomolecular screening, 10.1177/1087057108329348, 14, 3, 256-62, 2009.03, Monitoring and targeting protein kinases is widely accepted as a promising approach for disease diagnosis and drug discovery. For this purpose, the authors have developed an original type of peptide array as a high-throughput screening assay for quantitatively evaluating kinase activity. A volume of 2 nL of peptide solution was spotted onto a formyl group-modified glass slide by using an arrayer, which was designed for use with protein chip technology. The phosphorylation was recognized by fluorescence-label antibody and detected with an automatic microarray scanner widely used in DNA chip technology. The system needs low sample volume, provides a high-density peptide array, and supplies high reproducibility. It provided enough sensitivity for inhibitor screening, even though a relatively low concentration of purified kinase was employed. The assay also proved useful for the detection of intracellular kinase activity as well as for the measurement of the fluctuations of intracellular protein kinase activity with drug stimulation. Thus, this peptide array would be applicable for kinase-targeted diagnosis, cell-based drug screening, and signal pathway investigation..
160. Takahito Kawano, Yasuro Niidome, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, PNIPAM gel-coated gold nanorods for targeted delivery responding to a near-infrared laser., Bioconjugate chemistry, 10.1021/bc800480k, 20, 2, 209-12, 2009.02, Gold nanorods can be used as photothermal converters, permitting near-infrared (NIR) light to be transmitted deep into tissues without causing damage. We prepared hybrid nanorods with a core-shell structure, i.e., a single gold nanorod encapsulated in a poly (N-isopropylacrylamide) nanogel. Hybrid nanorods demonstrated remote, reversible, pulsatile phase transition and in vivo action after irradiation using a NIR laser..
161. T. Mori*, T. Hirano, A. Maruyama, Y. Katayama, T. Niidome, Y. Bnado, K. Ute, S. Takaku, Y. Maeda, Syndiotactic poly(N-n-propylacrylamide) shows highly cooperative phase transition, Langmuir, 25, 48-50, 2009.01.
162. Kentaro Sao, Masaharu Murata, Kaori Umezaki, Yuri Fujisaki, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Makoto Hashizume, Molecular design of protein-based nanocapsules for stimulus-responsive characteristics., Bioorganic & medicinal chemistry, 10.1016/j.bmc.2008.11.013, 17, 1, 85-93, 2009.01, Hsp16.5, a small heat-shock protein (sHSP) from hyperthermophilic archaeon, forms a homogeneous complex comprised of 24 subunits with a molecular mass of 400 kDa. This complex self-organizes under physiological conditions, and the structure of the complex is a nanoscale spherical capsule with small pores. Furthermore, this natural nanocapsule exhibits very high thermal stability. In this paper, we functionalized the nanocapsule to control the structure in response to external stimuli such as a protease signal and temperature. For this purpose, several mutations (Mut1-10) to create a cleavage site for a specific protease, Factor Xa, were introduced on the outer surface of the nanocapsule using a genetic engineering strategy. The resulting mutants were expressed to high levels in Escherichia coli. One of these mutants, Mut6, which has the most accessible cleavage site located at the triangular pore on the surface of the capsule, formed a spherical assembly similar to that observed for the wild-type protein. Mut6 showed the highest sensitivity to Factor Xa, and the structure of the protease digested Mut6 disassembled irreversibly after heating. In contrast, the nanocapsule comprising the wild-type Hsp16.5 was not influenced by the dual stimuli. These results suggest that Mut6 acts as a stimulus-responsive nanocapsule. Such a characteristic of the protein-based nanocapsule has attractive potential as a versatile intelligent system..
163. Takeshi Mori, Tomohiro Hirano, Atsushi Maruyama, Yoshiki Katayama, Takuro Niidome, Yoichi Bando, Koichi Ute, Shinji Takaku, Yasushi Maeda, Syndiotactic poly(N-n-propylacrylamide) shows highly cooperative phase transition., Langmuir : the ACS journal of surfaces and colloids, 10.1021/la8034837, 25, 1, 48-50, 2009.01, Syndiotactic poly(N-n-propylacrylamide)s (PNNPAM) with various racemo (r) diad contents were synthesized, and their phase transition behaviors were studied by high-sensitivity differential scanning calorimetry and FT-IR spectroscopy. The cooperativity of the phase transition increased with the increase in the r diad content. Compared with the atactic PNNPAM, the number of cooperative units, which shows the monomeric units length undergoing cooperative phase transition, increased 2.5- to 4-fold in the syndiotactic polymers. From the results of FT-IR spectroscopy and quantum chemical calculations, it was determined that the high cooperativity of the syndiotactic polymers resulted from local formation of an ordered structure in a dehydrated state..
164. Jeong-Hun Kang, Daisuke Asai, Jong-Hwan Kim, Takeshi Mori, Riki Toita, Tetsuro Tomiyama, Yoji Asami, Jun Oishi, Yuko T Sato, Takuro Niidome, Byungdug Jun, Hideki Nakashima, Yoshiki Katayama, Design of polymeric carriers for cancer-specific gene targeting: utilization of abnormal protein kinase Calpha activation in cancer cells., Journal of the American Chemical Society, 10.1021/ja805364s, 130, 45, 14906-7, 2008.11, We succeeded in cancer cell specific gene expression by using a polyplex responsive to protein kinase Calpha, which is activated in various types of cancer cells..
165. Mohamed R Berber, Keiji Minagawa, Masahiro Katoh, Takeshi Mori, Masami Tanaka, Nanocomposites of 2-arylpropionic acid drugs based on Mg-Al layered double hydroxide for dissolution enhancement., European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 10.1016/j.ejps.2008.08.006, 35, 4, 354-60, 2008.11, Naproxen (NP) and flurpibrofen (FB) as non-steroidal anti-inflammatory drugs (NSAIDs) of 2-arylpropionic acid derivatives have been used as host organic drugs to be intercalated into layered double hydroxide (LDH) applying reconstruction and co-precipitation techniques. The obtained NP-LDH and FB-LDH nanocomposites were characterized by X-ray powder diffraction, infrared and thermogravimetric analyses. From drug loading, thermal analysis and X-ray measurements we can decide that coprecipitaion technique is better than reconstruction technique to obtain intercalated monophase nanocomposites. In acidic medium LDH dissolved and the intercalated drug starts to release in a molecular form which is suitable for adsorption. The drug solubility has been investigated before and after intercalation. It has been found that LDH improves the drug solubility and its dissolution rate..
166. Jeong-Hun Kang, Daisuke Asai, Satoshi Yamada, Toita Riki, Jun Oishi, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Novel peptide is a protein kinase C (PKC)α-specific substrate, Proteomics, 2008.08.
167. Takuro Niidome, Yasuyuki Akiyama, Kohei Shimoda, Takahito Kawano, Takeshi Mori, Yoshiki Katayama, and Yasuro Niidome, In vivo monitoring of intravenously injected gold nanorods using near-infrared light, Small, 2008.07.
168. Jeong-Hun Kang, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, A syngeneic hepatocellular carcinoma model rapidly and simply prepared using a hydrodynamics-based procedure, Vet. J, 2008.07.
169. Jeong-Hun Kang,　Masanori Kuramoto, Akira Tsuchiya, Riki Toita, Daisuke Asai, Yuko T. Sato, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Correlation between phosphorylation ratios by MALDI-TOF MS analysis and enzyme kinetics, Eur. J. Mass Spectrom., , 2008.07.
170. Takuro Niidome, Yasuyuki Akiyama, Masato Yamagata, Takahito Kawano, Takeshi Mori, Yasuro Niidome, Yoshiki Katayama, PEG-modified gold nanorods as a photothermal nanodevice for hyperthermia, J. Biomater. Sci.-Polym. Ed, 2008.07.
171. Jun Oishi, Yoji Asami, Takeshi Mori, Jeong-Hun Kang, Takuro Niidome, Yoshiki Katayama, Colorimetric enzymatic activity assay based on "non-crosslinking aggregation" of gold nanoparticles induced by adsorption of substrate peptides, Biomacromolecules, 2008.07.
172. Tomohiro Hirano, Kimihiko Nakamura, Takahiro Kamikubo, Satoshi Ishii, Kanami Tani, Takeshi Mori, Tsuneyuki Sato, Hydrogen-bond-assisted syndiotactic-specific radical polymerizations of N-alkylacrylamides: The effect of the N-substituents on the stereospecificities and unusual large hysteresis in the phase-transition behavior of aqueous solution of syndiotactic poly(N-n-propylacrylamide), JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY, 10.1002/pola.22797, 46, 13, 4575-4583, 2008.07, The radical polymerizations of N-alkylacrylamides, such as N-methyl-(NMAAm), N-n-propyl-(NNPAAm), N-benzyl-(NBnAAm), and N-(1-phenylethyl)acrylamides (NPhEAAm), at low temperatures were investigated in the absence or presence of hexamethylphosphoramide (HMPA) and 3-methyl-3-pentanol (3Me3PenOH), which induced the syndiotactic specificities in the radical polymerization of N-isopropylacrylamide (NIPAAm). In the absence of the syndiotactic-specificity inducers, the syndiotacticities of the obtained polymers gradually increased as the bulkiness of the N-substituents increased. Both HMPA and 3Me3PenOH induced the syndiotactic specificities in the NNPAAm polymerizations as well as in the NIPAAm polymerizations. The addition of 3Me3PenOH into the polymerizations of NMAAm significantly induced the syndiotactic specificities, whereas the tacticities of the obtained polymers were hardly affected by adding HMPA. In the polymerizations of bulkier monomers, such as NBnAAm and NPhEAAm, HMPA worked as the syndiotactic specificity inducer at higher temperatures, whereas 3Me3PenOH hardly influenced the stereospecificity, regardless of the temperatures. The phase-transition behaviors of the aqueous solutions of poly(NNPAAm)s were also investigated. It appeared that the poly (NNPAAm) with racemo dyad content of 70% exhibited unusual large hysteresis between the heating and cooling processes. (C) 2008 Wiley Periodicals, Inc..
173. Jeong-Hun Kang, Daisuke Asai, Satoshi Yamada, Riki Toita, Jun Oishi, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, A short peptide is a protein kinase C (PKC) alpha-specific substrate., Proteomics, 10.1002/pmic.200701045, 8, 10, 2006-11, 2008.05, The purpose of this study was to find protein kinase C (PKC) isozyme-specific peptides. A peptide library containing 1772 sequences was designed using Scansite and screened by MALDI-TOF MS and kinase activity assays for PKC isozyme-specificity. A peptide (Alphatomega; H-FKKQGSFAKKK-NH(2)) with high specificity for PKC alpha relative to other isozymes was identified. The peptide was phosphorylated to a greater extent by tissue lysates from B16 melanoma, HepG2, and human breast cancer, which had higher levels of activated PKC alpha, when compared to normal skin, liver, and human breast tissue lysates, respectively. Moreover, addition of Ro-31-7549, an inhibitor with great specificity for PKC alpha, to the phosphorylation reaction caused a dose-dependent reduction in phosphorylation, but no inhibition was identified with the addition of rottlerin and H-89. These results show that this peptide has great potential as a PKC alpha-specific substrate..
174. Yusuke Inoue, Takeshi Mori, Go Yamanouchi, Xiaoming Han, Tatsuhiko Sonoda, Takuro Niidome, Yoshiki Katayama, Surface plasmon resonance imaging measurements of caspase reactions on peptide microarrays, Anal. Biochem., 375, 147-149 , 2008.04.
175. Kenjiro Ikuta, Takeshi Mori, Tatsuhiro Yamamoto, Takuro Niidome, Hiroaki Shimokawa, Yoshiki Katayama, Development of polymeric drug delivery system for recognizing vascular endothelial dysfunction, Bioorg. Med. Chem., 16, 2811-2818 , 2008.04.
176. Kenjiro Ikuta, Takeshi Mori, Tatsuhiro Yamamoto, Takuro Niidome, Hiroaki Shimokawa, Yoshiki Katayama, Development of polymeric drug delivery system for recognizing vascular endothelial dysfunction, Bioorg. Med. Chem., 16, 2811-2818 , 2008.04.
177. Takeshi Mori, Kazuki Inamori, Yusuke Inoue, Xiaoming Han, Go Yamanouchi, Takuro Niidome, Yoshiki Katayama, Evaluation of protein kinase activities of cell lysates using peptide microarrays based on surface plasmon resonance imaging., Analytical biochemistry, 10.1016/j.ab.2007.12.011, 375, 2, 223-31, 2008.04, We developed a peptide microarray based on surface plasmon resonance (SPR) imaging for monitoring protein kinase activities in cell lysates. The substrate peptides of kinases were tethered to the microarray surface modified with a self-assembled monolayer of an alkanethiol with triethylene glycol terminus to create a low nonspecific binding surface. The phosphorylation of the substrate peptides immobilized on the surface was detected with the following phosphate specific binders by amplifying SPR signals: anti-phosphotyrosine antibody for tyrosine kinases and Phos-tag biotin (a phosphate-specific ligand with biotin tag) for serine/threonine kinases. Using the microarray, 9 kinds of protein kinases were evaluated as a pattern of phosphorylation of 26 kinds of substrate peptides. The pattern was unique for each protein kinase. The microarray could be used to evaluate the inhibitory activities of kinase inhibitors. The microarray was applied successfully for kinase activity monitoring of cell lysates. The chemical stimuli responsive activity changes of protein kinases in cell lysates could also be monitored by the peptide microarray. Thus, the peptide microarray based on SPR imaging would be applicable to cell-based drug discovery, diagnosis using tissue lysates, and biochemical studies to reveal signal transduction pathways..
178. Jeong-Hun Kang, Daisuke Asai, Jun Oishi, Kenji Kawamura, Riki Toita, Yuhua Jiang, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, Role of plasma as activator and cofactor in phosphorylation by protein kinase C, Cell Biochem. Funct, 26, 70-75 , 2007.12.
179. Protein Kinase Assay Based on Aggregation of Gold Nanoparticles.
180. Jeong-Hun Kang, Yuko Sato, Riki Toita, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, ANYL 193-New method for in vivo imaging of intracellular signals and its application to cancer imaging, ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 234, 2007.08.
181. J. Oishi, Y. Asami, T. Mori*, J.-H. Kang, M. Tanabe, T. Niidome, Y. Katayama, Measurement of Homogeneous Kinase Activity for Cell Lysates Based on Aggregation of Gold Nanoparticles, ChemBioChem, 8, 875-879, 2007.06.
182. Measurement of homogeneous kinase activityfor cell lysates based on the aggregation of gold nanoparticles, Measurement of homogeneous kinase activityfor cell lysates based on the aggregation of gold nanoparticles, ChemBioChem, 8, 875-879, , 2007.05.
183. Xiaoming Han, Syuhei Shigaki, Takayuki Yamaji, Go Yamanouchi, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, A quantitative peptide array for evaluation of protein kinase activity, Anal. Biochem, 372, 106-115, 2007.04.
184. Takayuki Iida, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, Overall interaction of cytosolic proteins with the PEI/DNA complex., Journal of controlled release : official journal of the Controlled Release Society, 10.1016/j.jconrel.2006.12.027, 118, 3, 364-9, 2007.04, Little is known on mechanisms involved in transport of complex of DNA and gene carrier molecules from the cytosol to the nucleus. We aimed to identify cytosolic proteins interacting with the polyethylenimine (PEI)/DNA complex, using 2-D gel electrophoresis and peptide mass fingerprinting. Fifteen proteins including actin, beta-tubulin, and other metabolic proteins were identified. They demonstrated various molecular weights and isoelectric points, and were categorized into 3 groups: early binding, late binding, and transient binding proteins. Protein binding caused DNA release from the PEI/DNA complex with a cation/anion (C/A) ratio of 2, where complex formation was weak. Knowledge on interactions between cytosolic proteins and DNA/carrier complexes will help understand intracellular gene delivery mechanisms..
185. Syuhei Shigaki, Takayuki Yamaji, Xiaoming Han, Go Yamanouchi, Tatsuhiko Sonoda, Osamu Okitsu, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, A peptide microarray for the detection of protein kinase activity in cell lysate., Analytical sciences : the international journal of the Japan Society for Analytical Chemistry, 10.2116/analsci.23.271, 23, 3, 271-5, 2007.03, DNA microarray enables the analysis of DNA or mRNA expression levels, but it has not been possible to completely understand life using obtained information. Consequently, protein or peptide arrays have attracted much interest. Since the development of a practical protein microarray is still far away in light of handling difficulties, the peptide microarray is a promising tool for analyzing protein functions. We have developed a peptide microarray to detect protein kinase activity in cell lysate. All substrate peptides for kinases were immobilized chemoselectively on amino-coated glass slides. After phosphorylation of the immobilized peptides, phosphorylation was detected by fluorescence imaging. We detected the protein kinase activities, including that in cell lysate, in response to drug stimulation. Therefore, this peptide microarray would be useful for a high-throughput kinase assay of intracellular signals and would be applicable to drug screening..
186. Atsushi Shiotani, Takeshi Mori, Takuro Niidome, Yasuro Niidome, Yoshiki Katayama, Stable incorporation of gold nanorods into N-isopropylacrylamide hydrogels and their rapid shrinkage induced by near-infrared laser irradiation., Langmuir : the ACS journal of surfaces and colloids, 10.1021/la0627967, 23, 7, 4012-8, 2007.03, In this study, we prepared gold nanorod (NR)-embedded N-isopropylacrylamide (NIPAM) hydrogels and studied their volume phase transition behavior induced by near-infrared (near-IR) laser irradiation utilizing the photothermal conversion characteristics of the NRs. When poly(ethylene glycol)-modified NRs were used for the preparation of composite gels, the NRs showed marked dispersion stability in the gel. Near-IR laser irradiation of the gel (cylindrical shape, diameter = 140 microm) under the following conditions, NR concentrations in the gel > or =100 microM and laser irradiation power > or =490 mW, resulted in shrinkage of the gel in the following manner: (1) waist formation around the irradiation spot and (2) growth of the waist along the axial directions of the gel. The gel shrinking induced by near-IR irradiation occurred much more rapidly than that afforded by a temperature jump, because the former was not accompanied by the skin layer formation, which disturbs the rapid shrinking of the gels. When a composite gel containing the model drug (rhodamine-labeled dextran) was irradiated with a near-IR laser, the rapid release of the drug was observed. Taking advantage of the high spatial resolution of the irradiation point, we further achieved the irradiation-point-specific release of the drug from one such gel..
187. Takeshi Mori, Shiro Yasutake, Hideki Inoue, Keiji Minagawa, Masami Tanaka, Takuro Niidome, Yoshiki Katayama, "Threading" of beta-sheet peptides via radical polymerization., Biomacromolecules, 10.1021/bm060835n, 8, 2, 318-21, 2007.02, A nonamer peptide containing a diene group in the center of the sequence was synthesized. When the peptide forms an antiparallel beta-sheet, the diene groups align ca. 5 A apart on the beta-sheet. The diene groups successfully photopolymerized without distorting the beta-sheet structure. The obtained beta-sheet showed high stability against acid denaturation and addition of 1,1,1,3,3,3-hexafluoroisopropanol..
188. Takeshi Mori, Suguru Beppu, Isao Fukushima, Toru Kobayashi, Keiji Minagawa, Masami Tanaka, Takuro Niidome, Yoshiki Katayama, Temperature-responsive poly(dehydroalanine)s: Diversifying phase transition temperatures utilizing alpha,alpha-disubstituted motif, CHEMISTRY LETTERS, 10.1246/cl.2007.334, 36, 2, 334-335, 2007.02, The temperature-responsive poly(dehydroalanine derivative)s having two substituents at the alpha-position were successfully synthesized. By varying the combination of the structures of the two substituents, the relatively large diversity of their phase transition temperatures could be achieved..
189. Jeong-Hun Kang, Yoshiki Katayama, Aishan Han, Shuhei Shigaki, Jun Oishi, Kenji Kawamura, Riki Toita, Xiao Ming Han, Takeshi Mori, Takuro Niidome, Mass-tag technology responding to intracellular signals as a novel assay system for the diagnosis of tumor., Journal of the American Society for Mass Spectrometry, 10.1016/j.jasms.2006.09.004, 18, 1, 106-12, 2007.01, A novel mass spectrometry-based assay system for determining protein kinase activity employing mass-tagged substrate peptide probes was used for the diagnosis of tumors. Two peptide probes (H-type and D-type) were synthesized containing the same substrate peptide sequence for protein kinase C (PKC). The molecular weights of the two probes differ because of the incorporation of deuterium into the acetyl groups of the D-type probe. The lysates of the normal and tumor tissue were prepared and reacted with the H- and D-type peptide probes, respectively. The PKC activities of the normal and tumor tissues can be compared simply and directly by calculating the phosphorylated ratio to each peptide probe, obtained from the peak intensity of the mass spectrum after mixing of the two reaction solutions. The phosphorylation ratio for the reaction of the H-type peptide probe with the tumor tissue lysate (B16 melanoma) was more than three times higher than that of the D type peptide probe with the normal skin tissue lysate. These results show that the novel assay system for detecting protein kinase activity using mass-tag technology can be a simple and useful means to profile protein kinase activity for cell or tissue lysate samples, and can be applied to the diagnosis of tumors..
190. Masato Yamagata, Takahito Kawano, Kouhei Shiba, Takeshi Mori, Yoshiki Katayama, Takuro Niidome, Structural advantage of dendritic poly(L-lysine) for gene delivery into cells, BIOORGANIC & MEDICINAL CHEMISTRY, 10.1016/j.bmc.2006.09.033, 15, 1, 526-532, 2007.01, This study aimed to investigate the relationships between structures of gene carrier molecules and their activities for gene delivery into cells. We compared 2 types of poly(L-lysine) as carriers, that is, dendritic poly(L-lysine) (KG6) and linear poly(L-lysine) (PLL). KG6 formed a neutral DNA complex, and its DNA compaction level was weaker than that of PLL. The amount of DNA binding and uptake into cells mediated by PLL was 4-fold higher than that with KG6. However, KG6-mediated gene expression was 100-fold higher than that by PLL. Since pK(a) values of terminal amines of KG6 were lowered even though small amounts of DNA were internalized into cells, sufficient DNA amounts for effective gene expression escaped to the cytosol due to the proton sponge effect in the endosome. In addition, weakly compacted DNA with KG6 was advantageous in accessing RNA polymerase in the cell nucleus. On the other hand, PLL did not show the proton sponge effect in the endosome and resulted in strong compaction of DNA. Even though large DNA amounts were internalized into cells, most of the DNA would not take part in gene expression systems in the nucleus. Amount of induced cytokine production after intravenous injection of DNA complexes with KG6 and PLL was low, and was similar to the case when DNA was injected alone. Therefore, no significant difference in effects on cytokine production was observed between KG6 and PLL. (c) 2006 Elsevier Ltd. All rights reserved..
191. Jun Oishi, Moeko Ijuin, Tatsuhiko Sonoda, Jeong-Hun Kang, Kenji Kawamura, Takeshi Mori, Takuro Niidome, Yoshiki Katayama, A protein kinase signal-responsive gene carrier modified RGD peptide., Bioorganic & medicinal chemistry letters, 10.1016/j.bmcl.2006.08.096, 16, 22, 5740-3, 2006.11, We have previously reported artificial gene-regulation systems responding to cyclic AMP-dependent protein kinase (PKA) using a cationic polymer. However, this polymer alone cannot deliver any gene into living cells. In the present work, we modified the signal-responsive polymer to the RGD peptide for the introduction of a polymer/DNA complex into living cells and succeeded in regulating the gene expression responding to intracellular PKA activation..
192. Takeshi Mori, Yoichi Fukawa, Kenji Shimoyama, Keiji Minagawa, Polymerization of diacetylene using beta-sheet as a template, INTERNATIONAL JOURNAL OF MODERN PHYSICS B, 10.1142/S0217979206040519, 20, 25-27, 3872-3877, 2006.10, In the parallel and anti-parallel beta-sheet structures, hydrogen bonding arises between the amide bonds of the peptide chains to arrange them with a distance of ca. 5 angstrom. That distance matched with the repeating unit distance of polydiacetylene. In this study, the effectiveness of the beta-sheet as a template for the polymerization of diacetylene was examined by using diacetylene-introduced oligopeptides. The diacetylene-introduced amino acid (Thr(DA)) was synthesized from L-threonine. Though peptides Ac-Thr(DA)-NHMe and Ac-[Thr(DA)](2)-NHMe formed anti-parallel beta-sheet, they showed slight or no polymerization in both of the solid and the solution states. On the other hand, Ac-[Thr(DA)](5)-NHMe and 11mer peptide with a Thr(DA) in the center of the sequence contained anti-parallel beta-sheet structure and formed polydiacetylene of high degree of polymerization with high conversion during the cleavage process of the peptide from resin in the solution. This result indicated that the preorganization of the peptide through the beta-sheet formation was necessary for the polymerization of diacetylene group. Thus, the beta-sheet motif was effective template for the polymerization of diacetylene..
193. Keiji Minagawa, Yasunori Aoki, Takeshi Mori, Ternary electrorheological fluids with composite particles dispersed in liquid blends, INTERNATIONAL JOURNAL OF MODERN PHYSICS B, 10.1142/S0217979206040738, 20, 25-27, 3987-3992, 2006.10, The electrorheological (ER) properties were studied with ternary suspensions containing solid and liquid dispersoids in silicone oil (DMS). The solid dispersoid used was polyether/montmorillonite nanocomposite particles in which polyether molecules were intercalated between the layers of montmorillonite. The liquid dispersoid was urethane-modified polyether prepared from 4,4'-diphenylmethane diisocyanate (MDI) and poly(propylene glycol) (PPG). The steady shear viscosity and dynamic viscoelasticity were measured with a rotating parallel disc rheometer equipped with ER measurement system. The binary and ternary mixtures of these solid and liquid dispersoids with DMS, i.e. composite particle/DMS suspension, polyether/DMS liquid blend, and ternary blend containing both dispersoids, showed an increase of viscosity in response to an electric field (positive ER effect). The ER effect of a ternary suspension containing the particles and polyether liquids was larger than those of binary suspension or blend with one of these dispersoids. The ER effect was found to be improved by combination of the solid and liquid dispersoids, although the recovery time of viscosity after removing the electric field became rather longer, which would be due to the partly irreversible macroscopic aggregation of the dispersoids..
194. T. Mori, M. Nakashima, Y. Fukuda, K. Minagawa, M. Tanaka, Y. Maeda, Soluble-Insoluble-Soluble Transitions of Aqueous Poly(N-vinylacetamide-co-acrylic acid) Solutions, Langmuir, Vol. 22, No. 9, pp4336-4342, 2006.03.
195. T Mori, H Mori, K Minagawa, M Tanaka, Multi-step precipitation separation system using mixture of thermosensitive polymers, POLYMER BULLETIN, 10.1007/s00289-005-0486-y, 56, 2-3, 211-220, 2006.02, Multi-step precipitation separation system was developed by using aqueous mixtures of some thermosensitive polymers. The following three polymers were used here; poly(N-n-propylacrylamide), poly(N-isopropylacrylamide), and poly(N-isopropylmethacrylamide). A mixture of the three polymers showed three endothermic peaks, and the peak top temperatures were almost consistent with that of the each polymer solution. The polymers were purified by thermal precipitation to obtain fractions which can respond in narrow temperature ranges prior to use. In the case of the precipitation separation of two polymers mixtures, purities of the obtained precipitate and supernatant fractions became high comparing with the case in which the unpurified polymers were used. Parts of the polymers which were not the precipitation targets were also precipitated by the separation procedures. This was caused not only by insolubilization of the non-targeted polymers due to their phase transitions but also by their non-specific entanglement with the targeted polymers. The purities of the fractions also improved when the difference of the phase transition temperature between two polymers was large enough to avoid the coprecipitation. In the case of the precipitation separation of mixtures of the three polymers, purities of each fraction also improved when the purified polymers were used..
196. T. Mori, K. Yuyama, K. Narita, K. Minagawa, M. Haraguchi, M. Tanaka, Preparation of Nano- and Micro-Particles through Self-Assembly of Azobenzen-Pendent Ionomers, Journal of Applied Polymer Science, 2006.01.
197. J.-H. Kang, Y. Jiang, R. Toita, J. Oishi, K. Kawamura, A. Han, T. Mori, T. Niidome, M. Ishida, K. Tatematsu, K. Tanizawa, Y. Katayama, Phosphorylation of Rho-associated kinase (Rho-kinase/ROCK/ROK) substrates by protein kinases A and CPhosphorylation of Rho-associated kinase (Rho-kinase/ROCK/ROK) substrates by protein kinases A and C, Biochimie, in press, 2006.01.
198. T. Mori, M. Hamada, T. Kobayashi, H. Okamura, K. Minagawa, S. Masuda, M. Tanaka, Effect of Alkyl Substituents Structures and Added Ions on the Phase Transition of Polymers and Gels Prepared from Methyl 2-Alkylamidoacrylates, Journal of Polymer Science, Part A: Polymer Chemistry Edition, 2005.10.
199. T. Mori, T. Watanabe, K. Minagawa, M. Tanaka, Self-assembly of Oligo(p-phenylenevinylene)-block-Poly(ethylene oxide) in Polar Media and Solubilization of an Oligo(p-phenylenevinylene) Homooligomer inside the Assembly, Journal of Polymer Science, Part A: Polymer Chemistry Edition, Vol. 43, No.8, pp 1569-1578, 2005.04.
200. T. Mori, Y. Shiota, K. Minagawa, M. Tanaka, Alternative Approach to the Design of Thermosensitive Polymer: The Addition of Hydrophobic Groups to Ends of Hydrophilic Polyether, Journal of Polymer Science, Part A: Polymer Chemistry Edition, Vol. 43, No. 5, pp 1007-1013, 2005.03.
201. T. Mori, K. Shimoyama, Y. Fukawa, K. Minagawa, M. Tanaka, Parallel beta-sheet as a Novel Template for Polymerization of Diacetylene, Chemistry Letters, Vol. 34, No. 1, pp 116-117, 2005.01.
202. T. Mori, Y. Fukuda, H. Okamura, K. Minagawa, S. Masuda, M. Tanaka, Thermosensitive Copolymers Having Soluble and Insoluble Monomer Units, Poly(N-vinylacetamide-co-methyl acrylate)s: Effect of Additives on Their Lower Critical Solution Temperatures, Journal of Polymer Science, Part A: Polymer Chemistry Edition, Vol. 42, No. 11, pp 2651-2658, 2004.06.
203. T. Mori, M. Maeda, Temperature-Responsive Formation of Colloidal Nanoparticles from Poly(N-isopropylacrylamide) Grafted with Single-Stranded DNA, Langmuir, 10.1021/la0356194, 20, 2, 313-319, Vol. 20, No. 2, pp 313-319, 2004.01.
204. T. Mori, M. Maeda, Stability Change of DNA-Carrying Colloidal Particle Induced by Hybridization with Target DNA, Polymer Journal, 10.1295/polymj.34.624, 34, 8, 624-628, Vol. 34, No. 8, pp 624-628, 2002.08.
205. H. Okamura, Y. Morihara, S. Masuda, K. Minagawa, T. Mori, M. Tanaka, Effects of Salts and Copolymer Composition on Lower Critical Solution Temperature of Poly(methyl 2-acetamidoacrylate-co-methyl methacrylate) Solution, Journal of Polymer Science, Part A: Polymer Chemistry Edition, Vol. 40, No. 12, pp 1945-1951, 2002.06.
206. H. Okamura, T. Mori, K. Minagawa, S. Masuda, M. Tanaka, A Novel Thermosensitive Polymer, Poly(methyl 2-propionamidoacrylate), with Geminal Substituents, Polymer, Vol. 43, No. 13, pp 3825-3828, 2002.06.
207. H. Okamura, S. Masuda, K. Minagawa, T. Mori, M. Tanaka, Thermosensitive Properties of a Novel Poly(methyl 2-acetamidoacrylate-co-methyl acrylate), European Polymer Journal, Vol. 38, No. 4, pp 639-644, 2002.04.
208. H. Okamura, K. Suzuki, T. Mori, K. Minagawa, S. Masuda, M. Tanaka, Chain Behavior in Model Homogeneous ER Fluids Depending on Temperature, International Journal of Modern Physics B, Vol. 16, No. 17-18, pp 2385-2391, 2002.01.
209. K. Minagawa, K. Saitoh, H. Okamura, T. Mori, S. Masuda, M. Tanaka, Electric-Field Response of the Structure and Rheological Property of Silicone/Polyether Blends, International Journal of Modern Physics B, Vol. 16, Nos. 17-18, pp 2474-2480, 2002.01.
210. K. Minagawa, T. Kanno, H. Okamura, T. Mori, S. Masuda, H. Takagi, K. Koyama, M. Tanaka, Novel Electrorheological Materials with Ternary Blends Containing Polyethers and Urethanes, International Journal of Modern Physics B, Vol. 16, Nos. 17-18, pp 2481-2486, 2002.01.
211. H. Okamura, T. Maruyama, S. Masuda, K. Minagawa, T. Mori, M. Tanaka, A Novel Thermosensitive Poly(methyl 2-acetamidoacrylate), Journal of Polymer Research, Vol. 9, No. 1, pp 17-21, 2002.01.
212. T. Mori, D. Umeno, M. Maeda, Sequence-specific Affinity Precipitation of Oligonucleotide Using Poly(N-isopropylacrylamide) -Oligonucletide Conjugate, Biotechnolgy and Bioengineering, 10.1002/1097-0290(20010205)72:33.0.CO;2-7, 72, 3, 261-268, Vol. 72, No. 3, pp 261-268, 2001.02.
213. T. Mori, M. Maeda, Formation of DNA-Carrying Colloidal Particle from Poly(N-isopropylacrylamide)-graft-DNA Copolymer and Its Assembly through Hybridization, Polymer Journal, 33, 10, 830-833, Vol. 33, No. 10, pp 830-833, 2001.10.
214. J. Oishi, M. Ijuin, T. Sonoda, J.-H. Kang, K. Kawamura, T. Mori, T. Niidome, Y. Katayama, A protein kinase signal-responsive gene carrier modified RGD peptide, Bioorg. Med. Chem. Lett., in press.
215. Y. Otsubo, H. Ikeda, J. Kamimoto, T. Niidome, Takeshi Mori, Yoshiki Katayama, A Rapid and Quantitative Detection of Cellular Protein Kinase Activity Based on MALDI-TOF-MS, Chem. Lett., 43, 658.
216. C.W. Kim, D. Asai, J.-H. Kang, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama, Reversal of efflux of an anticancer drug in human drug-resistant breast cancer cells by inhibition of protein kinase C alpha activity, Tumor Biol.


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