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2004 Fiscal Year Final Research Report Summary

Creation of intelligent polymeric micelle nanocapsuls for gene delivery

Research Project

Project/Area Number 14380391
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

Principal Investigator

KATAOKA Kazunori  The University of Tokyo, School of Engineering, Professor, 大学院・工学系研究科, 教授 (00130245)

Co-Investigator(Kenkyū-buntansha) YAMASAKI Yuichi  The University of Tokyo, School of Engineering, Assistant Professor, 大学院・工学系研究科, 講師 (00322678)
SHIBA Mariko  Nationa Cardiovascular Center, Research Institute, laboratory Chief, 室長 (70271575)
Project Period (FY) 2002 – 2004
Keywordspolymeric micelle / gene delivery / block copolymer / nanocapsul / DNA / Biocompartibility / polyethylene glycol
Research Abstract

We investigated intelligent polymeric micelle nanocapsuls formed through the complexation of block copolymers and plasmid DNA, as non-viral gene vectors. The block copolymers are composed of a hydrophilic polyethylene glycol (PEG) and positively charged polyamino acids. To enhance the efficacy of gene expression, in particular in vivo system, novel strategy for the active targeting which can be realized through the introduction of pilot moiety on the surface of polymeric micelles should be established. For this purpose, we developed a synthetic scheme for block copolymers to employ multi-intelligent functions, i.e., prolonged circulation inside the blood vessel tubes, enhanced permeation from the blood vessel tubes toward tissues, selective transfection to the targeting tissues, enhanced cellular uptake due to the pilot moieties, smooth release of plasmid DNA inside the cells, etc.
In addition, a wide adaptability for the length of plasmid DNA and also the environmental responsibility of the polymeric micelle nanocapsuls that should be essential to overcome the efficacy of viral gene delivery system were experimentally conformed. This system exhibits highly transfection potency not only in in vitro system but also in preliminary in vivo experiments. This multi-intelligent polymeric micelle nanocapsuls can be treated as an universal platform of non-viral gene delivery system.

  • Research Products

    (32 results)

All 2005 2004 2003 2002

All Journal Article (32 results)

  • [Journal Article] Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotide with acid-labile linkage2005

    • Author(s)
      M.Oishi, S.Sasaki, Y.Nagasaki, K.Kataoka
    • Journal Title

      ChemBioChem 6(4)

      Pages: 718-725

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] PEGylated polyplex micelles from triblock catiomers with spatially-ordered layering of condensed pDNA and buffering units for enhanced intracellular gene delivery2005

    • Author(s)
      S.Fukushima, K.Miyata, N.Nishiyama, N.Kanayama, Y.Yamasaki, K.Kataoka
    • Journal Title

      J.Am.Chem.Soc. 127(9)

      Pages: 2810-2811

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lactosy-lated Poly(ethylene glycol)-siRNA conjugate through acid-labile β-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells2005

    • Author(s)
      M.Oishi, Y.Nagasaki, K.Itaka, N.Nishiyama, K.Kataoka
    • Journal Title

      J.Am.Chem.Soc. 127(6)

      Pages: 1624-1625

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Smart polyion complex micelles for targeted intracellular delivery of PEGylated antisense oligonucleotide with acid-labile linkage2005

    • Author(s)
      M.Oishi, S.Sasaki, Y.Nagasaki, K.Kataoka
    • Journal Title

      Chem Bio Chem (on the Web)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PEGylated Polyplex Micelles from Triblock Catiomers with Spatially Ordered Layering of Condensed pDNA and Buffeting Units for Enhanced Intracellular Gene Delivery2005

    • Author(s)
      S.Fukushima, K.Miyata, N.Nishiyama, N.Kanayama, Y.Yamasaki, K.Kataoka
    • Journal Title

      J.Amer.Chem.Soc. 127(9)

      Pages: 2810-2811

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Lactosylated Poly(ethylene glycol)-siRNA conjugate through acid-Labile β-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells2005

    • Author(s)
      M.Oishi, Y.Nagasaki, K.Itaka, N.Nishiyama, K.Kataoka
    • Journal Title

      J.Amer.Chem.Soc. 127(6)

      Pages: 1624-2625

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Polyion complex micelles of pDNA with acetal-poly(ethylene glycol)-poly(2-(dimethylamino)ethyl methacrylate) block copolymer as gene carrier systems : Physicochemical properties of micelles relevant to gene transfection efficacy2004

    • Author(s)
      D.Wakebayashi, N.Nishiyama, K.Itaka, K.Miyata, Y.Yamasaki, A.Harada, H.Koyama, Y.Nagasaki, K.Kataoka
    • Journal Title

      Biomacromolecules 5(6)

      Pages: 2128-2136

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Supramolecular nanocarrier of siRNA from PEG-based block catiomer carrying diamine side-chain with distinctive pKa directed to enhance intracellular gene silencing2004

    • Author(s)
      K.Itaka, N.Kanayama, N.Nishiyama, Y.Yamasaki, K.Nakamura, H.Kawaguchi, K.Kataoka
    • Journal Title

      J.Am.Chem.Soc. 126(42)

      Pages: 13612-13613

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Versatile Synthesis of End-functionalized Thermosensitive Poly(2-isopropyl-2-oxazolines)2004

    • Author(s)
      J.S.Park, Y.Akiyama, F.M.Winnik, K.Kataoka
    • Journal Title

      Macromolecules 37(18)

      Pages: 6786-6792

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Block copolymer-coated calcium-phosphate nanoparticles sensing intracellular environment for oligodeoxynucleotide and siRNA delivery2004

    • Author(s)
      Y.Kakizawa, S.Furukawa, K.Kataoka
    • Journal Title

      J. Controlled Release 97(2)

      Pages: 345-356

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Size-controlled formation of a calcium phosphate-based organic-inorganic hybrid vector for gene delivery using poly(ethylene glycol)-block-poly(aspartic acid)2004

    • Author(s)
      Y.Kakizawa, K.Miyata, S.Furukawa, K.Kataoka
    • Journal Title

      Advanced Materials 16(8)

      Pages: 699-702

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lactose-installed polyion complex micelles incorporating plasmid DNA as a targetable gene vector system : Their preparation and gene transfecting efficiency against cultured HepG2 cells2004

    • Author(s)
      D.Wakebayashi, N.Nishiyama, Y.Yamasaki, K.Itaka, N.Kanayama, A.Harada.Y.Nagasaki, K.Kataoka
    • Journal Title

      J. Controlled Release 95(3)

      Pages: 653-654

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Synthesis of heterotelechelic poly(ethylene glycol) derivatives having □-benzaldehyde and □-pyridyl disulfide groups by ring opening polymerization of ethylene oxide using 4-(diethoxymethyl)benzyl alkoxide as a novel initiator2004

    • Author(s)
      Y.Akiyama, Y.Nagasaki, K.Kataoka
    • Journal Title

      Bioconjugate Chemistry 15(2)

      Pages: 424-427

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Block catiomer polyplexes with regulated densities of charge and disulfide cross-linking directed to enhance gene expression2004

    • Author(s)
      K.Miyata, Y.Kakizawa, N.Nishiyama, A.Harada, Y.Yamasaki, H.Koyama, K.Kataoka
    • Journal Title

      J.Am.Chem.Soc. 126(8)

      Pages: 2355-2361

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Microcalorimetric Study of the Temperature-Induced Phase Separation in Aqueous Solutions of Poly(2-isopropyl-2-oxazolines)2004

    • Author(s)
      C.Diab, Y.Akiyama, K.Kataoka, F.M.Winnik
    • Journal Title

      Macromolecules 37(7)

      Pages: 2556-2562

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effective accumulation of polyion complex micelle to experimental choroidal neovascularization in rats2004

    • Author(s)
      R.Ideta, Y.Yanagi, Y.Tamaki, F.Tasaka.A.Harada, K.Kataoka
    • Journal Title

      FEBS Lett. 557(1-3)

      Pages: 21-25

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In situ single cell observation by fluorescence resonance energy transfer reveals fast intra-cytoplasmic delivery and easy release of plasmid DNA complexed with linear polyethylenimine2004

    • Author(s)
      K.Itaka, A.Harada, Y.Yamasaki, K.Nakamura, H.Kawaguchi, K.Kataoka
    • Journal Title

      J. Gene Med. 6(1)

      Pages: 76-84

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Supramolecular nanocarrier of siRNA from PEG-based block catiomer carrying diamine side-chain with distinctive pKa directed to enhance intracellular gene silencing2004

    • Author(s)
      K.Itaka, N.Kanayama, N.Nishiyama, Y.Yamasaki, K.Nakamura, H.Kawaguchi, K.Kataoka
    • Journal Title

      J.Amer.Chem.Soc. 126(42)

      Pages: 13612-13613

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Block copolymer-coated calcium-phosphate nanoparticles sensing intracellular environment for oligodeoxynucleotide and siRNA delivery2004

    • Author(s)
      Y.Kakizawa, S.Furukawa, K.Kataoka
    • Journal Title

      J.Controlled Release 97(2)

      Pages: 345-356

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Lactose-installed polyion complex micelles incorporating plasmid DNA as a targetable gene vector system : Their preparation and gene transfecting efficiency against cultured HepG2 cells2004

    • Author(s)
      D.Wakebayashi, N.Nishiyama, Y.Yamasaki, K.Itaka, N.Kanayama, A.Harada, Y.Nagasaki, K.Kataoka
    • Journal Title

      J.Controlled Release 95(3)

      Pages: 653-664

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synthesis of heterotelechelic poly(ethylene glycol) derivatives having α-benzaldehyde and ω-pyridyl disulfide groups by ring opening polymerization of ethylene oxide using 4-(diethoxymethyl)benzyl alkoxide as a novel initiator2004

    • Author(s)
      Y.Akiyama, Y.Nagasaki, K.Kataoka
    • Journal Title

      Bioconjugate Chemistry 15(2)

      Pages: 424-427

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Block catiomer polyplexes with regulated densities of charge and disulfide cross-linking directed to enhance gene expression2004

    • Author(s)
      K.Miyata, Y.Kakizawa, N.Nishiyama, A.Harada, Y.Yamasaki, H.Koyama, K.Kataoka
    • Journal Title

      J.Amer.Chem.Soc. 126(8)

      Pages: 2355-2361

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Microcalorimetric Study of the Temperature-Induced Phase Separation in Aqueous Solutions of Poly(2-isopropyl-2-oxazolines)2004

    • Author(s)
      C.Drab, Y.Akiyama, K.Kataoka, F.M.Winnik
    • Journal Title

      Macromolecules 37(7)

      Pages: 2556-2562

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Effective accumulation of polyion complex micelle to experimental choroidal neovascularization in rats2004

    • Author(s)
      R.Ideta, Y.Yanagi, Y.Tamaki, F.Tasaka, A.Harada, K.Kataoka
    • Journal Title

      FEBS Lett. 557(1-3)

      Pages: 21-25

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] In situ single cell observation by fluorescence resonance energy transfer reveals fast intra-cytoplasmic delivery and easy release of plasmid DNA complexed with linear polyethylenimine2004

    • Author(s)
      K.Itaka, A.Harada, Y.Yamasaki, K.Nakamura, H.Kawaguchi, K.Kataoka
    • Journal Title

      J.Gene Med. 6(1)

      Pages: 76-84

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PEG-PLL block copolymers induce reversible large discrete coil-globule transition in a single DNA molecule through cooperative complex formation2003

    • Author(s)
      Y.Yamasaki, S.Katayose, K.Kataoka, K.Yoshikawa
    • Journal Title

      Macromolecules 36(16)

      Pages: 6276-6279

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Effect of charged segment length on physicochemical properties of core-shell type polyion complex micelles from block ionomers2003

    • Author(s)
      A.Harada, K.Kataoka
    • Journal Title

      Macromolecules 36(13)

      Pages: 4995-5001

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] pH-Responsive Oligodeoxynucleotide (ODN)-Poly(Ethylene Glycol) Conjugate through Acid-Labile β-Thiopropionate Linkage : Preparation and Polyion Complex Micelle Formation2003

    • Author(s)
      M.Oishi, S.Sasaki, Y.Nagasaki, K.Kataoka
    • Journal Title

      Biomacromolecules 4(5)

      Pages: 1426-1432

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Polyion complex micelles from plasmid DNA and poly(ethylene glycol)-poly(L-lysine) block copolymer as serum-tolerable polyplex system : Physicochemical properties of micelles relevant to gene transfection efficiency2003

    • Author(s)
      K.Itaka, K.Yamauchi, A.Harada, K.Nakamura, H.Kawaguchi, K.Kataoka
    • Journal Title

      Biomaterials 24(24)

      Pages: 4495-4506

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Lactose-installed poly(ethylene glycol)-poly(D, L-lactide) block copolymer micelles exhibit fast-rate binding and high affinity towards a protein bed simulatin (g a cell surface. A surface plasmon resonance study2003

    • Author(s)
      E.Jule, Y.Nagasaki, K.Kataoka
    • Journal Title

      Bioconjugate Chemistry 14(1)

      Pages: 177-186

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A surface plasmon resonance study on the interaction between lactose-installed poly(ethylene glycol)-poly(D, L-lactide) block copolymer micelles and lectins immobilized on a gold surface2002

    • Author(s)
      E.Jule, Y.Nagasaki, K.Kataoka
    • Journal Title

      Langmuir 18(26)

      Pages: 10334-10339

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A surface plasmon resonance study on the interaction between lactose-installed polyethylene glycol)-poly(D, L-lactide) block copolymer micelles and lectins immobilized on a gold surface2002

    • Author(s)
      E.Jule, Y.Nagasaki, K.Kataoka
    • Journal Title

      Langmuir 18(26)

      Pages: 10334-10339

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

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Published: 2006-07-11  

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