2007 Fiscal Year Final Research Report Summary
Development of functional polymeirc micelles responding to intracellular microenvironments for cancer chemotherapy
| Project/Area Number |
17200031
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biological material science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KATAOKA Kazunori The University of Tokyo, Graduate School of Engineering, Professor (00130245)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Yuichi The University of Tokyo, Graduate School of Engineering, Associate Professor (00322678)
NISHIYAMA Nobuhiro The University of Tokyo, Graduate School of Medicine, Associate Professor (10372385)
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| Project Period (FY) |
2005 – 2007
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| Keywords | drug delivery / polymeric micelles / cancer chemotherapy / chemotherapeutic agents / environment sensitivity / cancer targeted therapy / nanotechnology |
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| Research Abstract |
Polymeric micelles, the self-assemblies of block copolymers, are a promising nanocarrier system for drug delivery. Indeed, several formulations have been studied in clinical trials. Polymeric micelles are characterized by a size of several tens nm and unique core-shell structure, where the drug-loaded core is surrounded by biocompatible poly(ethylene glycol) (PEG) chains. These characteristics of polymeric micelles allow their longevity in the bloodstream and effective tumor accumulation after their systemic administration. In this project, we have prepared pH-sensitive polymeric micelles, in which adriamycin (ADR) is attached to the side chain of the core-forming segment of the block copolymers via an acid-labile hydrazone bond. The system showed appreciable drug release under intracellular low pH conditions, while exhibiting no drug release under physiological pH conditions. We applied such pH-sensitive polymeric micelles for the treatment of pancreatic cancers, which are known to be intractable due to hypovascularity and thick fibrosis. As a result, pH-sensitive polymeric micelles showed significant antitumor efficacy against subcutaneous pancreatic cancers in mice. Meanwhile, the pH-sensitive micelles were modified with a folate molecule to construct the polymeric micelles with the tumor-targetability. A large number of cancer cells are known to overexpress folate-binding proteins (FBP). The folate-conjugated micelles were more efficiently taken up by the FBP-overexpressing cancer cells, achieving remarkable antitumor effect at much lower ADR concentrations than the non-targeted micelles. These results indicate that the use of the folate-conjugated micelles may lower the effective doses over free ADR, improving the safety of the clinical chemotherapy. Thus, functional pH-sensitive polymeric micelles developed in this study are expected to improve the safety and efficacy of the treatments against intractable malignant tumors.
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Research Products
(108 results)
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[Journal Article] Dendrimer generation effects on photodynamic efficacy of dendrimer porphyrins and dendrimer-loaded supramolecular nanocarriers2007
Author(s)
Y. Li, W. -D. Jang, N. Nishiyama, A. Kishimura, S. Kawauchi, Y. Morimoto, S. Miake, T. Yamashita, M. Kikuchi, T. Aida, K. Kataoka
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Journal Title
Chem. Mater. 19(23)
Pages: 5557-5562
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Improvement of cancer-targeting therapy, using nanocarriers for intractable solid tumors by inhibition of TGF-beta signaling2007
Author(s)
M. R. Kano, Y. Bae, C. Iwata, Y. Morishita, M. Yashiro, M. Oka, T. Fujii, A. Komuro, K. Kiyono, M. Kamiishi, K. Hirakawa, Y. Ouchi, N. Nishiyama, K. Kataoka, K. Miyazono
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Journal Title
Proc. Natl. Acad. Sci. USA. 104(9)
Pages: 3460-3465
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Iron hydroxide nanoparticles coated with poly (ethylene glycol)-poly (aspartic acid) block copolymer as novel magnetic resonance agents for in vivo cancer imaging2007
Author(s)
M. Kumagai, Y. Imai, T. NAkamura, Y. Yamasaki, M. Sekino, S. Ueno, K. Hanaoka, K. Kikuchi, T. Nagano, E. Kaneko, K. Shimokado, K. Kataoka
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Journal Title
Colloids Surf., B Biointerfaces 56
Pages: 174-181
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer2005
Author(s)
N. Nishiyama, A. Iriyama, W. -D. Jang, K. Miyata, K. Itaka, Y. Inoue, H. Takahashi, Y. Yanagi, Y. Tamaki, H. Koyama, K. Kataoka
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Journal Title
Nature Mater 4(12)
Pages: 934-341
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumour activity and reduce the neurotoxicity of paclitaxel2005
Author(s)
T. Hamaguchi, Y. Matsumura, M. Suzuki, K. Shimizu, R. Goda, I. Nakamura, I. Nakatomi, M. Yokoyama, K. Kataoka, T. Kakizoe
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Journal Title
Br. J. Cancer 92
Pages: 1240-1246
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Supramolecular nanocarrier of anionic dendrimer porphyrins with cationic block copolymers modified with poly (ethylene glycol) to enhance ntracellular photodynamic efficacy2005
Author(s)
W. -D. Jang, N. Nishiyama, G. -D. Zhang, A. Harada, D. -L. Jiang, S. Kawauchi, Y. Morimoto, M. Kikuchi, H. Koyama, T. Aida, K. Kataoka, K. Kataoka
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Journal Title
Angew. Chem. Int. Ed. 44(3)
Pages: 419-423
Description
「研究成果報告書概要(欧文)」より
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