人工細胞質設計に向けた液液相分離モデル系の構築と濃厚環境の機能的理解
キーワード:コアセルベート、細胞内相分離、タンパク質
2019.06~2021.03.



岸村 顕広(きしむら あきひろ) | データ更新日:2019.06.21 |

主な研究テーマ
生体内での自律駆動を目指した自発光型ナノシステム創製とその応用
キーワード:光源フリー、ナノメディシン、ベシクル
2017.04~2019.07.
キーワード:光源フリー、ナノメディシン、ベシクル
2017.04~2019.07.
ナノ構造化コアセルベートを用いた新規ソフトマテリアル基盤の確立
キーワード:コアセルベート、ブロック共重合体、ポリイオンコンプレックス、ハイブリッド材料、タンパク質
2015.04.
キーワード:コアセルベート、ブロック共重合体、ポリイオンコンプレックス、ハイブリッド材料、タンパク質
2015.04.
分子集合体型薬物ナノカプセルの内部物性制御に基づく体内動態制御
キーワード:ドラッグデリバリーシステム、ナノメディシン、薬物動態学、ナノ生理学
2018.04~2022.03.
キーワード:ドラッグデリバリーシステム、ナノメディシン、薬物動態学、ナノ生理学
2018.04~2022.03.
高分子ナノカプセルを用いた生体内における新規酵素利用基盤の構築
キーワード:酵素、ナノメディシン、タンパク質デリバリー、ベシクル、ナノリアクター
2014.04~2017.03.
キーワード:酵素、ナノメディシン、タンパク質デリバリー、ベシクル、ナノリアクター
2014.04~2017.03.
クラウディング・ナノコンパートメントの創製とナノリアクターとしての開発
キーワード:ナノコンパートメント、ベシクル、分子クラウディング、酵素反応
2013.04~2015.03.
キーワード:ナノコンパートメント、ベシクル、分子クラウディング、酵素反応
2013.04~2015.03.
研究業績
主要著書
主要原著論文
1. | Beob Soo Kim, Sayan Chuanoi, Tomoya Suma, Yasutaka Anraku, Kotaro Hayashi, Mitsuru Naito, Hyun Jin Kim, Ick Chan Kwon, Kanjiro Miyata, Akihiro Kishimura, Kazunori Kataoka, Self-Assembly of siRNA/PEG- b-Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules, Journal of the American Chemical Society, 10.1021/jacs.8b13641, 141, 8, 3699-3709, 2019.02, [URL], Vesicular polyion complexes (PICs) were fabricated through self-assembly of rigid cylindrical molecules, small interfering RNAs (siRNAs), with flexible block catiomers of poly(ethylene glycol) (2 kDa) and cationic polyaspartamide derivative (70 units) bearing a 5-aminopentyl side chain. 100 nm-sized siRNA-assembled vesicular PICs, termed siRNAsomes, were fabricated in specific mixing ranges between siRNA and block catiomer. The siRNAsome membrane was revealed to consist of PIC units fulfilling a simple molar ratio (1:2 or 2:3) of block catiomer and siRNA. These ratios correspond to the minimal integer molar ratio to maximally compensate the charge imbalance of PIC, because the numbers of charges per block catiomer and siRNA are +70 and -40, respectively. Accordingly, the ζ-potentials of siRNAsomes prepared at 1:2 and 2:3 were negative and positive, respectively. Cross-section transmission electron microscopic observation clarified that the membrane thicknesses of 1:2 and 2:3 siRNAsomes were 11.0 and 17.2 nm, respectively. Considering that a calculated long-axial length of siRNA is 5.9 nm, these thickness values correspond to the membrane models of two (11.8 nm) and three (17.7 nm) tandemly aligned siRNAs associating with one and two block catiomers, respectively. For biological application, siRNAsomes were stabilized through membrane-cross-linking with glutaraldehyde. The positively charged and cross-linked siRNAsome facilitated siRNA internalization into cultured cancer cells, eliciting significant gene silencing with negligible cytotoxicity. The siRNAsome stably encapsulated dextran as a model cargo macromolecule in the cavity by simple vortex mixing. Confocal laser scanning microscopic observation displayed that both of the payloads were internalized together into cultured cells. These results demonstrate the potential of siRNAsomes as a versatile platform for codelivery of siRNA with other cargo macromolecules.. |
2. | Mao Hori, Horacio Cabral, Kazuko Toh, Akihiro Kishimura, Kazunori Kataoka, Robust Polyion Complex Vesicles (PICsomes) under Physiological Conditions Reinforced by Multiple Hydrogen Bond Formation Derived by Guanidinium Groups, Biomacromolecules, 10.1021/acs.biomac.8b01097, 19, 10, 4113-4121, 2018.10, [URL], Polyion complex vesicles (PICsomes) formed from a self-assembly of an oppositely charged pair of block- and homo-polyelectrolytes have shown exceptional features for functional loading of bioactive agents. Nevertheless, the stability of PICsomes is often jeopardized in a physiological environment, and only PICsomes having chemically cross-linked membranes have endured in harsh in vivo conditions, such as in the bloodstream. Herein, we developed versatile PICsomes aimed to last in in vivo settings by stabilizing their membrane through a combination of ionic and hydrogen bonding, which is widely found in natural proteins as a salt bridge, by controlled introduction of guanidinium groups in the polycation fraction toward concurrent polyion complexation and hydrogen bonding. The guanidinylated PICsomes were successfully assembled under physiological salt conditions, with precise control of their morphology by tuning the guanidinium content, and the ratio of anionic and cationic components. Guanidinylated PICsomes with 100 nm diameter, which are relevant to nanocarrier development, were stable in high urea concentration, at physiological temperature, and under serum incubation, persisting in blood circulation in vivo.. |
3. | Masamitsu Suhara, Yutaka Miura, Horacio Cabral, Daisuke Akagi, Yasutaka Anraku, Akihiro Kishimura, Masaya Sano, Takuya Miyazaki, Noriko Nakamura, Ayako Nishiyama, Kazunori Kataoka, Hiroyuki Koyama, Katsuyuki Hoshina, Targeting ability of self-assembled nanomedicines in rat acute limb ischemia model is affected by size, Journal of Controlled Release, 10.1016/j.jconrel.2018.07.049, 286, 394-401, 2018.09, [URL], Peripheral artery disease (PAD) is one of the most spreading diseases all over the world. The treatment strategies are limited to surgical or endovascular procedures for final stage chronic PAD or acute limb ischemia, and no pharmacological approaches have been achieved to prevent the worsening of chronic PAD or to regenerate the tissues of acute limb ischemia. Therefore, the improvement of therapeutic strategy is strongly demanded in clinics. Here, we adopted an acute hindlimb ischemia model in rats, which provides concomitant inflammatory response, to evaluate the application of drug delivery system against PAD. Through comparative experiments by using different-sized nanomedicine analogues, polyion complex (PIC) micelles with 30 nm diameter and PIC vesicles with 100- and 200-nm diameter (PICs-30, −100, −200 respectively), we found the size-dependent accumulation and retention in the collateral arteries. In contrast to PICs-30 and -200, histological analysis showed that PICs-100 were around the arterioles and co-localized with macrophages, which indicates that the PICs-100 can achieve moderate interaction with phagocytes. Our data suggests that controlling the size of nanomedicines has promise for developing novel angiogenic treatments toward the effective management of collateral arteries.. |
4. | Omer F. Mutaf, Yasutaka Anraku, Akihiro Kishimura, Kazunori Kataoka, Unilamellar polyion complex vesicles (PICsomes) with tunable permeabilities for macromolecular solutes with different shapes and sizes, Polymer, 10.1016/j.polymer.2017.10.062, 133, 1-7, 2017.12, [URL], Polyion complex vesicles (PICsomes) are characterized by their unique three-layered semipermeable nanomembrane structures, in which a unilamellar PIC layer is sandwiched by poly(ethylene glycol) layers, and have gathered much attention as nano-scaled drug vehicles. Herein, the crosslinking degree of the nanomembrane in the PICsome was controlled systematically for the first time. Permeability of the PICsome nanomembrane was evaluated through a kinetic study of the release of macromolecular cargoes from the PICsome. The degree of crosslinking in the nanomembrane successfully regulated the release behavior. Moreover, the shape and size of the macromolecular solutes were found to be critical factors determining their transport from the inner aqueous phase of the PICsome to the external environment. The results indicate that the unique three-layered structure of PICsome membranes plays a key role in modulating solute transport. These findings will provide a rational strategy for the development of nanomembrane-based controlled-release systems.. |
5. | Hengmin Tang, Takeshi Mori, Yoshiki Katayama, Akihiro Kishimura, Development of Enzyme Loaded Polyion Complex Vesicle (PICsome): Thermal Stability of Enzyme in PICsome compartment and Effect of Co-Encapsulation of Dextran on Enzyme Activity., Macromolecular Bioscience, 10.1002/mabi.201600542, 2017.05. |
6. | Akihiro Kishimura, Akinori Goto, Ping-Shan Lai, Kazunori Kataoka, Facile Preparation of Delivery Platform of Water-Soluble Low-Molecular-Weight Drugs Based on Polyion Complex Vesicle (PICsome) Encapsulating Mesoporous Silica Nanoparticle, ACS Biomaterials Science & Engineering, 10.1021/acsbiomaterials.6b00562, 2017.03. |
7. | Akihiro Kishimura, Naoki Sasaki, Kae Sato, A Membrane-Integrated Microfluidic Device to Study Permeation of Nanoparticles through Straight Micropores toward Rational Design of Nanomedicines, Analytical Science, 10.2116/analsci.32.1307, 32, 12, 1307-1314, 2016.12. |
8. | Kenshiro Naoyama, Takeshi Mori, Yoshiki Katayama, Akihiro Kishimura, Fabrication of Dendrimer-based Polyion Complex Submicrometer-scaled Structures with Enhanced Stability under Physiological Conditions., Macromolecular Rapid Communications, 10.1002/marc.201600171, 37, 13, 1087-1093, 2016.05. |
9. | Akihiro Kishimura, Yutaka Miura, Hiroyuki Koyama, Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries., Molecular Pharmaceutics (ACS), 10.1021/acs.molpharmaceut.6b00219, 13, 6, 2108-2116, 2016.05. |
10. | Akihiro Kishimura, Systemically Injectable Enzyme-loaded Polyion Complex Vesicles (PICsomes) as in vivo Nanoreactors Working in Tumor., Angewandte Chemie International Edition, 10.1002/anie.201508339, 55, 560-565, 2016.01, The design and construction of nanoreactors are important for biomedical applications of enzymes, but lipid- and polymeric-vesicle-based nanoreactors have some practical limitations. We have succeeded in preparing enzyme-loaded polyion complex vesicles (PICsomes) through a facile protein- loading method. The preservation of enzyme activity was confirmed even after cross-linking of the PICsomes. The cross- linked b-galactosidase-loaded PICsomes (beta-gal@PICsomes) selectively accumulated in the tumor tissue of mice. Moreover, a model prodrug, HMDER-betaGal, was successfully converted into a highly fluorescent product, HMDER, at the tumor site, even 4days after administration of the beta-gal@PICsomes. Intravital confocal microscopy showed continuous production of HMDER and its distribution throughout the tumor tissues. Thus, enzyme-loaded PICsomes are useful for prodrug activation at the tumor site and could be a versatile platform for enzyme delivery in enzyme prodrug therapy.. |
11. | Akihiro Kishimura, Induction of Secondary Structure through Micellization of an Oppositely Charged Pair of Homochiral Block- and Homopolypeptides in an Aqueous Medium, Macromol. Rapid Commun, 10.1002/marc.201500368, 2015.08. |
12. | Akihiro Kishimura, Density-tunable conjugation of cyclic RGD ligands with polyion complex vesicles for the neovascular imaging of orthotopic glioblastomas, SCIENCE AND TECHNOLOGY OF ADVANCED MATERIALS, 10.1088/1468-6996/16/3/035004, 16, 3, 2015.06. |
13. | Akihiro Kishimura, Fabrication of polyion complex vesicles with enhanced salt and temperature resistance and their potential applications as enzymatic nanoreactors., American Chemical Society, 10.1021/bm500127g, 15, 7, 2389-2397, 2014, 2014.07. |
14. | Akihiro Kishimura, Morphology Control in Water of Polyion Complex Nanoarchitectures of Double-Hydrophilic Charged Block Copolymers through Composition Tuning and Thermal Treatment. , American Chemical Society, 10.1021/ma500314d , 47, 9, 3086-3092, 2014, 2014.04. |
15. | Akihiro Kishimura, Polyion complex vesicles for photo-induced intracellular delivery of amphiphilic photosensitizer., J. Am. Chem. Soc., 10.1021/ja406992w, 136, 1, 157-163, 2014, 2013.11. |
主要総説, 論評, 解説, 書評, 報告書等
1. | 岸村顕広, 「好き」で科学者になれる社会をつくるために, 化学、2019, 74 (5), 11., 2019.05. |
2. | 新福洋子、岸村顕広, 若手アカデミーから見た科学的助言, 学術の動向、2019、24 (3)、52–55., 2019.03. |
3. | 加藤千尋、岸村顕広、新福洋子、住井英二郎、中西和嘉、西嶋一欽、松中 学、安田仁奈、狩野光伸、, 若手科学者による座談会 –ブダペスト宣言の精神は、今後どう展開するのか, 学術の動向、2019、24 (1)、42–57., https://doi.org/10.5363/tits.24.1_42, 2019.01, [URL]. |
4. | 岸村顕広, SDGsから考える学術の社会貢献 –若手アカデミーの視点から, https://doi.org/10.5363/tits.23.8_16, 2018.08, [URL]. |
5. | 岸村顕広, 若手アカデミーの国際的活動を通じて思う「日本の国際的プレゼンス拡大」、学術の動向, 学術の動向、2018、23 (10)、64-70., https://doi.org/10.5363/tits.23.10_64, 2018.10, [URL]. |
6. | 岸村顕広, ポリイオンコンプレックス形成による簡便なポリマーナノ構造形成技術の開発と機能材料への応用, 化学工業, 2018.05. |
7. | 岸村 顕広, エマージングマテリアル・PICsome 〜PEGとPEGのはざまで〜, Drug Delivery System, 2016.09. |
8. | 岸村 顕広, 静電相互作用を利用したポリアミノ酸由来高分子電解質のユニークな自己組織化とその生体材料応用, 自己組織化マテリアルのフロンティア (フロンティア出版), 2015.12. |
9. | 岸村 顕広, 高分子中空ナノカプセルPICsomeの作製法とその活用, DDSキャリア作製プロトコル集、株式会社シーエムシー出版:東京, 2015.08. |
10. | Akihiro Kishimura, Horacio Cabral, Kanjiro MIyata, Nanodevices for studying nano-pathophysiology, Advanced Drug Delivery reviews, DOI: 10.1016/j.addr.2014.06.003, 2014.06, Nano-scaled devices are a promising platform for specific detection of pathological targets, facilitating the anal- ysis of biological tissues in real-time, while improving the diagnostic approaches and the efficacy of therapies. Herein, we review nanodevice approaches, including liposomes, nanoparticles and polymeric nanoassemblies, such as polymeric micelles and vesicles, which can precisely control their structure and functions for specifically interacting with cells and tissues. These systems have been successfully used for the selective delivery of reporter and therapeutic agents to specific tissues with controlled cellular and subcellular targeting of biomolecules and programmed operation inside the body, suggesting a high potential for developing the analysis for nano- pathophysiology.. |
11. | Akihiro Kishimura, ポリイオンコンプレックス型透過膜を有する中空カプセルPICsomeの開発とその応用, 膜, 2014.09. |
12. | Akihiro Kishimura, Development of polyion complex vesicles (PICsomes) from block copolymers for biomedical applications, Polymer Journal, 2013.04, Polyion complex (PIC) formation is one of the most powerful techniques for obtaining molecular self-assemblies in aqueous media. The simple preparation process based on multiple electrostatic interactions is quite attractive for material syntheses, as well as biomedical applications. Therefore, it is desirable to control PIC architectures at the nanoscale in order to expand the scope of PIC materials. In this review article, recent progress on PIC vesicles (PICsomes) is summarized. PICsomes were first developed by my research group, and we recently succeeded in controlling the sizes and structural uniformity of the vesicles. Furthermore, the characteristic dynamic nature of PICs was revealed: PICs were found to exhibit reversible association/ dissociation and structural transformation. We demonstrated that crosslinking the PIC layers of PICsomes is a powerful method for tuning properties such as stability and permeability. Finally, the potential utility of PICsomes for drug delivery nanocarriers was examined, and their future biomedical application is discussed.. |
主要学会発表等
その他の優れた研究業績
2018.06, 高分子ミセルの放出が可能な温度応答性徐放担体設計の新手法.
2018.11, siRNAを膜成分として含有するベシクル型ポリイオンコンプレックス(siRNAsome)の構築とsiRNAデリバリーへの展開.
2017.03, 酵素封入型ナノリアクターによる生理活性物質の除去に基づく病態制御法開発:生体内ヒスタミン分解・除去機能の評価.
学会活動
所属学会名
日本バイオマテリアル学会
日本DDS学会
Controlled Release Society
American Chemical Society
一般社団法人 日本MRS
公益社団法人 高分子学会
公益社団法人 日本化学会
公益社団法人 日本薬学会
学協会役員等への就任
2019.03~2020.02, 日本化学会九州支部, 幹事.
2017.12~2020.09, 第24期日本学術会議若手アカデミー, 代表.
2017.02, the Global Young Academy (GYA), Member.
学会大会・会議・シンポジウム等における役割
2015.12.09~2015.12.10, 第25回日本MRS年次大会, シンポジウムオーガナイザー.
2016.12.19~2016.12.20, 第26回日本MRS年次大会, シンポジウムオーガナイザー.
2017.12.05~2017.12.06, 第27 回日本MRS年次大会, シンポジウムオーガナイザー.
2018.12.18~2018.12.20, 第28 回日本MRS年次大会 , シンポジウムオーガナイザー.
2017.12.14~2017.12.16, The 2nd International Symposium on Biofunctional Chemistry (ISBC2017), Scientific Program Committee .
2017.08.20~2017.08.24, Biomaterials International 2017 (BMI2017), Organizing Committee.
2017.03.16~2017.03.16, 日本化学会第97春季年会・特別企画9「生命化学が先導する分子機能創成の最先端:生体機能・生体分子を超えるためのアプローチ」, 企画責任者、セッションオーガナイザー.
2017.01.17~2017.01.17, 日本化学会エキゾチック自己組織化材料 (ExOM) & 九大分子システム科学センター (CMS) 第1回合同シンポジウム, 企画責任者・世話人.
2016.11.21~2016.11.22, 日本バイオマテリアル学会シンポジウム2016, 実行委員.
2015.09.18~2015.09.18, 第5回日本バイオマテリアル学会九州ブロック講演会, 実行委員.
2014.06.13~2014.06.14, 第7回NanoBio若手ネットワーキングシンポジウム, 世話人.
2014.08.01~2014.08.01, 第1回ソフト界面研究会, 組織委員.
2014.08~2013.08, IUMRS-ICA2014, セッションオーガンナイザー.
2014.09.24~2014.09.26, 第63回高分子討論会 特定テーマ14.“動き”のある自己組織化材料:動的応答・変化を示す材料の設計・機能・応用の最前線, セッションオーガナイザー.
2015.01.20~2015.01.20, The 2nd CMS International Symposium, シンポジウムオーガナイザー.
学術論文等の審査
年度 | 外国語雑誌査読論文数 | 日本語雑誌査読論文数 | 国際会議録査読論文数 | 国内会議録査読論文数 | 合計 |
---|---|---|---|---|---|
2018年度 | 7 | 7 | |||
2017年度 | 15 | 15 | |||
2016年度 | 9 | 9 | |||
2013年度 | 6 | 6 | |||
2014年度 | 10 | 10 | |||
2015年度 | 18 | 18 |
その他の研究活動
海外渡航状況, 海外での教育研究歴
華中科技大学, China, 2016.05~2016.05.
国立中興大学, 中央研究院, Taiwan, 2018.10~2018.10.
Insitut Teknologi Bandung (ITB), Indonesia, 2016.10~2016.10.
Westfälische Wilhelms-Universität Münster, RWTH Aachen University, Germany, 2016.08~2016.09.
西北農林科技大学, China, 2016.10~2016.10.
中南民族大学, 華中科技大学, China, 2016.05~2016.05.
Bristol大学, UnitedKingdom, 2015.07~2015.07.
外国人研究者等の受入れ状況
2018.07~2018.08, 2週間以上1ヶ月未満, Department of Material Engineering, Faculty of Mechanical and Aerospace Engineering (FMAE), Institute of Technology, Bandung (ITB); Research Center for Nanoscience and Nanotechnology (RCNN), ITB, Indonesia, 外国政府・外国研究機関・国際機関.
2015.06~2015.08, 1ヶ月以上, 延世大学大学院理学部化学科, Japan, 外国政府・外国研究機関・国際機関.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2019年度~2019年度, 基盤研究(C), 分担, ナノ薬剤評価用マイクロ腫瘍組織モデルの開発.
2018年度~2019年度, 挑戦的研究(萌芽), 分担, RNA膜で構成される人工エクソソームの創製と高機能生理活性メディエーターへの展開.
2018年度~2021年度, 基盤研究(B), 代表, 分子集合体型薬物ナノカプセルの内部物性制御に基づく体内動態制御.
2017年度~2018年度, 挑戦的研究(萌芽), 代表, 生体内での自律駆動を目指した自発光型ナノシステムの創製とその応用.
2011年度~2013年度, 基盤研究(B), 分担, 超分子デバイスと光技術を駆使した微小がんの一期的な診断・治療システムの開発.
2014年度~2016年度, 基盤研究(B), 代表, 高分子ナノカプセルを用いた生体内における新規酵素利用基盤の構築.
2011年度~2013年度, 若手研究(A), 代表, 高分子ベシクルを用いた人工オルガネラの創製と細胞内配置技術の開発.
2013年度~2015年度, 新学術領域研究, 代表, ポリイオンコンプレックスナノ構造を中心とする融合マテリアル創出法の開発.
2013年度~2015年度, 挑戦的萌芽研究, 代表, クラウディング・ナノコンパートメントの創製とナノリアクターとしての開発.


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