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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
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
KeywordsBlock copolymer / Polymer micelle / DNA / Gene vector / Polyion complex / Luciferese assay / Gene delivery / ポリエチレングリコール / ポリアミノ酸 / ヌクレアーゼ
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.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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
    • Related Report
      1999 Final Research Report Summary
  • [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 Charaged Block Copolymers"Macromolecules. 32(20). 6892-6894 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] A. Harada, K. Kataoka: "On-off control of enzymatic activity synchoronizing with reversible formation of supramolecular assembly from enzyme and charged block copolymers"J. Amer. Chem. Soc.. 121(39). 9241-9242 (1999)

    • Related Report
      1999 Annual Research Report
  • [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"Clloids and Surfaces B : Biointerfaces. 16(1-4). 135-146 (1999)

    • Related Report
      1999 Annual Research Report
  • [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)

    • Related Report
      1999 Annual Research Report
  • [Publications] K. Kakizawaa, 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)

    • Related Report
      1999 Annual Research Report
  • [Publications] A. Harada, H. Togawa, K. Kataoka: "Physicochemical Properties and Nuclease Resistance of Antisense-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).

    • Related Report
      1999 Annual Research Report
  • [Publications] 片岡 一則: "高分子の自己組織化を利用した人工ウイルスベクターの開発"遺伝子医学. 16 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Harada: "Chain length recognition: Core-shell supramolecular assembly from oppositely charged block copolymers" Science. 283. 65-67 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Kataoka: "Effect of the secondary structure of poly(L-lysine) segments on the micellization in aqueous miheu of poly(ethylene glycol)-poly(L-lysine)block copolymer partially substituted with a hydrocinnamoyl-group at the N-position" Macromolecules. 31. 6071-6076 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Y.Nagasaki: "Tailored Polymeric Materials for Controlled Delivery Systems(ACS Symp.Ser.709)" American Chemical Society,Washington,D.C., 105-116 (1998)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] SKatayose, K.Kataoka: "Remarkable increase in nuclease resistance of plasmide DNA through supramolecular assembly with poly(ethylene gycol)-poly(L-lysine)block copolymer" J.Pharm.Sci.87(2). 160-163 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] A.Harada, K.Kataoka: "Formation of stabale and monodispersive polyion complex micelles in aqueous medium from poly(L-lysine)and poly(ethylene glycol)-poly(aspartic acid)block copolymer" J.Macromol.Sci,Pure Appl.Chem.A32(10). 2119-2133 (1997)

    • Related Report
      1997 Annual Research Report
  • [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)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.B.La, K.Kataoka, et al: "Poly(ethylene glycol): Chemistry and Biological Application (ACS Symposium Series 680)" American Chemical Society, 489 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Kataoka, et al: "Controlled Drug Delivery: Challenges and Strategies" American Chemical Society, 629 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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