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1999 Fiscal Year Final Research Report Summary

Preparation and evaluation of block copolymer micelle for novel gene vector

Research Project

Project/Area Number 09480258
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionThe University of Tokyo (1998-1999)
Tokyo University of Science (1997)

Principal Investigator

KATAOAKA Kazunori  Department of Materials Science, University of Tokyo, Professor, 大学院・工学系研究科, 教授 (00130245)

Co-Investigator(Kenkyū-buntansha) CHIBA Jyo  Department of biotechnology, Science University of Tokyo, Professor, 基礎工学部, 教授 (30100085)
Project Period (FY) 1997 – 1999
KeywordsBlock copolymer / Polymer micelle / DNA / Gene vector / Polyion complex / Luciferese assay / Gene delivery
Research Abstract

Specific targeting of therapeutic agents including peptide and gene has received a considerable impetus for effective therapy of various diseases, especially cancer. This study is aimed to develop novel vehicle system for gene targeting to achieve longevity in blood circulation, and eventually to deliver gene into target cells with high efficiency. Inspired by the nanometric-scaled core-shell structure of virus, stable and monodispersive micelles with gene-loading core were prepared through a self-assembly of poly (ethylene glycol)-poly (L-lysine) block copolymer (PEG-P(L-lysine) based oh electrostatic attraction. Plasmid DNA became highly resistant against nuclease attack by packing into the micelle core surrounded by a palisade of hydrophilic segments. From a viewpoint of utilizing these micelles as non-viral gene vector, the regulated release of DNA from the micelle is essential to achieve effective transfection. DNA release from the micelles in the cytoplasm may proceed through the exchange with the anionic compounds such as sulfated sugar. The reversible nature of PEG-P (L-lysine)/DNA micelle was further verified through the addition of polyanion, including dextran sulfate and poly-L-aspartic acid : polyanion replaced DNA in the complex with PEG-P(L-lysine), resulting in the release of free DNA in the medium. Transfection efficiency of the micelle toward cultured cells was then evaluated by luciferase assay. The micelles with excess PEG-P(L-lysine) showed an order of magnitude increase in the transfection efficiency compared to free as well as P(L-lysine)-associated plasmid DNA, indicating a promising feature of PEG-P(L-lysine)/DNA micelles as novel non-viral gene vectors. Further, various functional groups can be installed on the outer surface of the micelle so as to fix guiding molecules for a target site in the body. These results clearly featured a feasibility of polymer micelles as novel virus-inspired vehicles for gene delivery.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] S. Katayose, K. Kataoka: "Water-soluble polyion complex associates of DNA and poly(ethylene glycol)-p(L-lysine) blick copolymer"Bioconjugate Chemistry. 8(5). 702-707 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Katayose, K. Kataoka: "Remarkable increase in nuclease resistance of plasmid DNA through supramolecular assembly with poly(ethylene glycol)-poly(L-lysine)block copolymer"J. Pharmaceutical Sciences. 87(2). 160-163 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Kataoka, A. Harada, D. Wakebayashi, Y. Nagasaki: "Polyion Complex Micelles with Reactive Aldehyde Groups on Their Surface from Plasmid DNA and End-Functionalized Charged Block Copolymers"Macromolecules. 32(20). 6892-6894 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Yasugi, T. Nakamura, Y. Nagasaki, M.Kato, K.Kataoka: "Sugar-installed Polymer Micelles : Synthesis and Micellization of Poly(ethylene glycol)-Poly(D,L-lactide) Block Copolymers Having Sugar Groups at PEG Chain End"Macromolecules. 32(24). 8024-8032 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Kakizawa, A. Harada, K. Kataoka: "Environment-sensitive stabilization of core-shell structured polyion complex micelle by reversible cross-linking of the core through disulfide bond"J. Amer. Chem. Soc.. 121(48). 11247-11248 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A. harada, H.Togawa, K.Kataoka: "Physicochemical Properties and Nuclease Resistance of Anitisense-Oligonucleotides Entrapped in the Core of Polyion Complex Micelles Composed of Poly(ethylene glycol)-Poly(L-lysine) Block Copolymers"Eur. J. Pharm. Sci.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] L. W. Seymour, K. Kataoka, A. V. Kabanov: "Cationic block copolymers as self-assembling vectors for gene delivery"Self-Assembling Complexes for Gene Delivery, John Wiley. 21 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 片岡一則: "高分子ミセル型ベクターによる細胞内遺伝子導入"日本臨床. 6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Cammas, T. Matsumoto, T. Okano, Y. Sakurai, K. Kataoka: "Design of functional polymeric micelles as site-specific drug vehicles based on poly (α-hydroxy ethylene oxid-co-β-benzyl L-aspartate) block copolymers"Materials Science & Engineering C : Biomimetic Materials, Sensors and Systems. 4. 241-247 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Katayose, K. Kataoka: "Water-soluble polyion complex associates of DNA and poly(ethylene glycol)-P(L-lysine) block copolymer"Bioconjugate Chemistry. 8(5). 702-707 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Harada and K. Kataoka: "Formation of stable and monodispersive polyion complex micelles in aqueous medium from poly(L-lysine) and poly(ethylene glycol)-poly(aspartic acid) block copolymer"J. Macormol. Sci., Pure Appl. Chem.. A34(10). 2119-2133 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Harada, K. Kataoka: "Novel polyion complex micelles entrapping enzyme molecules in the core : Preparation of narrowly-distributed micelles from lysozyme and poly(ethylene glycol)-poly(aspartic acid) block copolymer in aqueous medium"Macromolecules. 31(2). 288-294 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Katayose, K. Kataoka: "Remarkable increase in nuclease resistance of plasmid DNA through supramolecular assembly with poly(ethylene glycol)-poly(L-lysine) block copolymer"J. Pharmaceutical Sciences. 87(2). 160-163 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T. Nakamura, Y. Nagasaki, K. Kataoka: "Synthesis of heterobifunctional PEG with a reducing monosaccharide residue at one end"Bioconjugate Chemistry. 9(2). 300-303 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Nagasaki, T. Okada, C. Scholz, M. Iijima, M. Katao, K. Kataoka: "The reactive polymeric micelle based on an aldehyde-ended poly(ethylene glycol)/poly(lactide) block copolymer"Macromolecules. 31(5). 1473-1479 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Kataoka, A. Ishihara, A. Harada, H. Miyazaki: "Effect of the secondary structure of poly(L-lysine) segments on the micellization in aqueous milieu of poly(ethylene glycol)-poly(L-lysine) block copolymer partially substituted with a hydrocinnamoyl-group at the Nε-position"Macromolecules. 31(18). 6071-6076 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] C. Scholz, M. Iijima, Y. Nagasaki, K. Kataoka: "Polymeric micelles as drug delivery systems : A reactive polymeric micelle carrying aldehyde groups"Polym. Adv. Tech. 9. 1-9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Liaw, T. Aoyagi, K. Kataoka, Y. Sakurai, T. Okano: "Visualization of PEO-PBLA-pyrene polymeric micelles by atomic force microscopy"Pharmaceutical Research. 15(11). 1721-1726 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Harada, K. Kataoka: "Chain length recognition : Core-shell supramolecular assembly from oppositely charged block copolymers"Science. 283(5398). 65-67 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J. Liaw, T. Aoyagi, K. Kataoka, Y. Sakurai, T. Okano: "Permeation of PEO-PBLA-FITC polymeric micelles in aortic endothelial cells"Pharmaceutical Research. 16(2). 213-220 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Harada, K. Kataoka: "Novel polyion complex micelles entrapping enzyme molecules in the core [II] : Characterization of the micelles prepared at non-stoichiometric mixing ratios"Langmuir. 15(12). 4208-4212 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Kataoka, A. Harada, D. Wakebayashi, Y. Nagasaki: "Polyion complex micelles with reactive aldehyde groups on their surface from plasmid DNA and end-functionalized charged block copolymers"Macromolecules. 32(20). 6892-6894 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Harada, K. Kataoka: "On-off regulation of enzymatic activity synchronizing with reversible formation of supramolecular assembly from enzyme and charged block copolymers"J. Amer. Chem. Soc.. 121(39). 9241-9242 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Yamamoto, Y. Nagasaki, M. Kato, K. Kataoka: "Surface charge modulation of poly(ethylene glycol-poly(D, L-lactide) block copolymer micelles : Conjugation of charged peptides"Colloids and Surfaces B : Biointerfaces. 16(1-4). 135-146 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Yasugi, Y. Nagasaki, M. Kato, K. Kataoka: "Preparation and characterization of polymer micelles from poly(ethylene glycol)-poly(d, l-lactide) block copolymer as potential drug carrier"J. Controlled Release. 62(1-2). 89-100 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Yasugi, T. Nakamura, Y. Nagasaki, M. Kato, K. Kataoka: "Sugar-installed polymer micelles : synthesis and micellization of poly(ethylene glycol)-poly(D, L-lactide) block copolymers having sugar groups at PEG chain end"Macromolecules. 32(24). 8024-8032 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y. Kakizawa, A. Harada, K. Kataoka,: "Environment-sensitive stabilization of core-shell structured polyion complex micelle by reversible cross-linking of the core through disulfidebond"J. Amer. Chem. Soc.. 121(48). 11247-11248 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A. Harada, H. Togawa, K. Kataoka: "Physicochemical properties and nuclease resistance of antisense-oligodeoxynucleotides entrapped in the core of polyion complex micelles composed of poly(ethylene glycol)-poly(L-lysine) block copolymers"Eur. J. Pharm. Sci.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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