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Exploiting Neomycin-RNA complexation to create PIC micelle based efficient transportation for therapeutic siRNA

Research Project

Project/Area Number 16K12904
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine

Principal Investigator

Quader Sabina  公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), 川崎市産業振興財団, 主任研究員 (90749699)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsNeomycin / PolyIionComplex / siRNA / polymer / Aminoglycoside / Polyion Complex / cancer / Nucleic Acid / RNA-binding / aminoglycosides / PIC micelle / anticancer / combination-therapy
Outline of Final Research Achievements

The aim of this research is to construct PolyIonComplex (PIC), where, a widely used amimoglycoside antibiotic Neomycin, that has specific RNA-binding ability and also has anti-angiogenin property, will be used as polycationic segments to hold polyanionic siRNA or other nucleic acids for cancer-therapy. To achieve this purpose we designed a novel polymer conjugated with azide functionalized neomycin through click chemistry between the azide function of neomycin and alkyne function of polymer. Alkyne function was introduced in poly(ethylene glycol)-b-poly(β-benzyl-aspartamide) polymer via aminolysis reaction utilizing propargyl amine. We utilized dual armed PEG with each arm having molecular weight of around 40 KD and with only 6 repeating units of poly amino acid segments. This polymer was designed to conjugate calculated no of Neomycin units so to construct PolyIonComplex with minimum molar ratio of polymer and thus ultimately achieve very small size (around 25 nm) PIC.

Report

(2 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (8 results)

All 2018 2017

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Nanomaterial-Enabled Cancer Therapy2017

    • Author(s)
      Sabina Quader, Kazunori Kataoka
    • Journal Title

      Molecular Therapy

      Volume: 25 Issue: 7 Pages: 1501-1513

    • DOI

      10.1016/j.ymthe.2017.04.026

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Proteasome inhibitor loaded micelles enhance antitumor activity through macrophage reprograming by NF-κB inhibition"2017

    • Author(s)
      Hailiang Wu, Anqi Tao, John D. Martin, Sabina Quader, Xueying Liu, Kei Takahashi, Louise Hespel, Yutaka Miura, Yoshihiro Hayakawa, Tatsuro Irimura, Horacio Cabral, Kazunori Kataoka
    • Journal Title

      J. Pharm. Sci,

      Volume: - Issue: 9 Pages: 30217-30224

    • DOI

      10.1016/j.xphs.2017.03.031

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effective treatment of drug resistant recurrent breast tumors harboring cancer stem-like cells by staurosporine/epirubicin co-loaded polymeric micelles2017

    • Author(s)
      J. Zhang, H. Kinoh, L. Hespel, X. Liu, S. Quader, J. Martin, T. Chida, H. Cabral, K. Kataoka,
    • Journal Title

      Journal of Controlled Release, "Vol. 264, pp. 127-1335, 2017

      Volume: 264 Pages: 127-135

    • DOI

      10.1016/j.jconrel.2017.08.025

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] cRGD peptide-installed epirubicin-loaded polymeric micelles for effective targeted therapy against brain tumors2017

    • Author(s)
      S. Quader, X. Liu, Y. Chen, P. Mi, T. Chida, T. Ishii, Y. Miura, N. Nishiyama, H. Cabral, K. Kataoka
    • Journal Title

      J. Control. Release

      Volume: 258 Pages: 56-66

    • DOI

      10.1016/j.jconrel.2017.04.033

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Targeting cancer using stimuli-sensitive polymeric micelle2018

    • Author(s)
      Sabina Quader, Kazunori Kataoka
    • Organizer
      International Symposium on Biorelated Polymers: 255th ACS National Meeting.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tuning the Drug Release Kinetics of pH-responsive Polymer Micelle to achieve better therapy outcome in Glioblastoma model.2018

    • Author(s)
      Sabina Quader, Xueying Liu, Hiraoki Kinoh, Kazunori Kataoka
    • Organizer
      67th SPSJ Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nanocarrier system for cancer therapy2017

    • Author(s)
      Sabina Quader
    • Organizer
      Summer School Nanosciences, Fundamental and Applications Emphasizing in Nanomedicine. Institute of Technology Bandung, Indonesia.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Safe and effective transport of anti-cancer drug, thru pH-sensitive polymeric micelle.2017

    • Author(s)
      Sabina Quader, Xueying Liu, Horacio Cabral, Kazunori Kataoka
    • Organizer
      66th SPSJ Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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