| Arihiro Kano | Last modified date：2012.6.16 |
Associate Professor /
Department of Integrated Materials
Institute for Materials Chemistry and Engineering
Institute for Materials Chemistry and Engineering
Graduate School
Undergraduate School
E-Mail
Homepage
http://www.cm.kyushu-u.ac.jp/wmaruyama/.
Phone
092-802-2520
Academic Degree
Ph. D.
Field of Specialization
Cell Biology, Molecular Biology, Polymer Chemistry
Outline Activities
1. Interferon-gamma (IFN-gamma), an inflammatory cytokine, is a potent apoptosis inducer for hepatocytes. We have shown that the IFN-gamma-induced apoptosis is mediated by anti-tumor factors, such as p53 and IRF-1. We are now developing new type drugs on the basis of the mechanism of IFN-gamma-induced apoptosis, other than the basic study of the apoptosis. These results would contribute to understand the machinery of inflammatory diseases of liver and establish the method of remedy for them. We study sinusoidal endothelial cells of liver (LSEC). We have revealed that the activation of immune cells are controlled by LSEC. This finding has let us work on developing of the methods for treatment to allergies, against pollen, egg, and so on, by the technique of delivery of allergen to LSEC, and through the study of the function of LSEC. And yet we study the mechanisms of LSEC to control immune responses.
2. Delivery carriers for therapeutic agents, including gene and nucleic acid medicine, have the great ability to provide revolutionary disease treatments. A large number of studies have been performed for this aim using liposome, micelle, gel, polymer, and virus-mediated techniques. Liposome and micelle are self-assembled and size-controllable nano particles. These properties are preferable to encapsulate polar or lipophilic drugs, whereas liposome and micelle are often not stable enough in blood circulation. Unlike the lipid carrier, hydrophilic polymeric material itself normally determines the size of the complex with its lords. Therefore molecular weight and steric effects of polymeric material should be considered. Poly-L-lysine (PLL) is a biocompatible polymer consisted with cationic peptides. Such cationic polymers interact with negatively charged DNA or RNA and form a complex, so-called polyplex. Therefore cationic polymers have been widely studied for gene therapy as a non-viral carrier. Although positive charges are needed for polyplex formation and the interaction to cell membranes to be internalized into the cell, these are also bound to plasma proteins and quickly cleared from the circulation. In this study, we employed PLL as a carrier backbone and grafted hydrophilic linear polymer as a side chain to prevent unwanted interactions and provide specific targeting activities. For these objects, we chose hyaluronan (HA), a linear poly saccharide that is known to be metabolized in liver, and poly(ethylene glycol) (PEG) to examine the effect of hydrophilic side chains grafted on PLL as a carrier for drugs and genes. Additionally, the ε-amine group of PLL is thought to be a reactive moiety for interaction to other therapeutic agents, not only for ionic interaction to DNA or RNA. Based on this consideration, we also examined the effect of ε-amine group on biodistribution of PLL-g-PEG after the intravenous injection in mice.
2. Delivery carriers for therapeutic agents, including gene and nucleic acid medicine, have the great ability to provide revolutionary disease treatments. A large number of studies have been performed for this aim using liposome, micelle, gel, polymer, and virus-mediated techniques. Liposome and micelle are self-assembled and size-controllable nano particles. These properties are preferable to encapsulate polar or lipophilic drugs, whereas liposome and micelle are often not stable enough in blood circulation. Unlike the lipid carrier, hydrophilic polymeric material itself normally determines the size of the complex with its lords. Therefore molecular weight and steric effects of polymeric material should be considered. Poly-L-lysine (PLL) is a biocompatible polymer consisted with cationic peptides. Such cationic polymers interact with negatively charged DNA or RNA and form a complex, so-called polyplex. Therefore cationic polymers have been widely studied for gene therapy as a non-viral carrier. Although positive charges are needed for polyplex formation and the interaction to cell membranes to be internalized into the cell, these are also bound to plasma proteins and quickly cleared from the circulation. In this study, we employed PLL as a carrier backbone and grafted hydrophilic linear polymer as a side chain to prevent unwanted interactions and provide specific targeting activities. For these objects, we chose hyaluronan (HA), a linear poly saccharide that is known to be metabolized in liver, and poly(ethylene glycol) (PEG) to examine the effect of hydrophilic side chains grafted on PLL as a carrier for drugs and genes. Additionally, the ε-amine group of PLL is thought to be a reactive moiety for interaction to other therapeutic agents, not only for ionic interaction to DNA or RNA. Based on this consideration, we also examined the effect of ε-amine group on biodistribution of PLL-g-PEG after the intravenous injection in mice.
Research
Research Interests
Membership in Academic Society
- Search for immunoregulatory substances by splenocyte culture system
keyword : Immune Suppression, Splenocytes, LPS, Liver Sinusoidal Endothelial cells, Cancer cells
2008.04～2021.06. - Complex formation of the tumor-directed graft polymer and anticancer agents and its application to the cancer therapy
keyword : water soluble macromolecule, DDS, photo dynamic therapy
2008.04. - Analysis of the dynamics of water soluble macromolecules in vivo and application to tumor therapy
keyword : water soluble macromolecule, DDS, EPR
2007.04～2011.03. - Delivery of siRNA to tumors by passive targetting
keyword : siRNA, PLL-PEG, EPR
2005.04～2009.10. - The role of liver in immune response and its control
keyword : liver, liver sinusoidal endothelial cell, immunology, hyaluronan
2003.04. - Analysis of apoptosis induced by IFN-gamma
keyword : Hepatocyte, Interferon-gamma, Apoptosis, SV40 large T antigen,
2002.04. - Conditional knockout mice of STAT3
keyword : STAT-3, Knockout mouse, Endothelial cell, Endotoxin, Immune suppression
1998.09～2002.02.
Papers
| 1. | Kano A., Wolfgang M.J., Gao Q., Jacoby J., Chai G.X., Hansen W., Iwamoto Y, Pober J.S., Flavell R.A., Fu XY.,Endothelial cells require STAT3 for protection against endotoxin-induced inflammation.,J Exp Med.,198, 1517-1525,2003.01. |
| 2. | Welte T., Zhang S.S., Wang T., Zhang Z., Hesslein D.G., Yin Z., Kano A., Iwamoto Y., Li E., Craft J.E., Bothwell A.L., Fikrig E., Koni P.A., Flavell R.A., Fu XY.,STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality,Proc Natl Acad Sci U S A.,100, 1879-84,2003.01. |
| 3. | Kano A., Haruyama T., Akaike T., Watanabe Y.,IRF-1 is an essential mediator in IFN-gamma-induced cell cycle arrest and apoptosis of primary cultured hepatocytes. Biochem Biophys Res Commun.,Biochem Biophys Res Commun.,121, 677-683.,1999.01. |
- Japanese Society for Biomaterials
- The Society of Polymer Science, Japan
- The Molecular Biology Society of Japan
- The Japanese Biochemical Society
- The Japan Society of Drug Delivery System
- Controlled Release Society
Educational
Educational Activities
Plan, teaching, and marking of the practice for under graduate students.
Teaching and guiding for the thesis for master degree and graduation.
Other Educational Activities
Teaching and guiding for the thesis for master degree and graduation.
- 2010.06,The 9th China-Japan-Korea Foresight Joint Symposium on Gene Delivery and the International Workshop on Biomaterials 2010 was held in Changchun. This symposium was financially supported by Japan Society for the Promotion of Science. I worked on it as an executive committee in the Japanese side. Fourteen Japanese resercher and one graduate student were sent to this sympoium. .
- 2010.07,Young Exchange Seminar for A3 Foresight Program that was held in Korea Advanced Institute of Science and Technology, Daejeon, Korea, from July 4 to 7, 2010, by the financial support of Japan Society for the Promotion of Science, JSPS. For this 4-day meeting, 10 graduate students, including from Kumamoto university were sent. I essentially contributed to this project. .
Social
Professional and Outreach Activities
Based on an agreement among JSPS, Korea Science and Engineering Foundation(KOSEF) and National Natural Science Foundation of China(NSFC), this program supports joint research conducted by researchers of Japan, China and Korea. The three countries(A3) work as consortium in advancing leading-edge research with an aim to establishing a top- level research hub in Asia.(Started from FY2005.)
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