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

2017 Fiscal Year Annual Research Report

• Project/Area Number: 16K12904
• Research Institution: Kawasaki 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), ナノ医療イノベーションセンター, 主任研究員 (90749699)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: Aminoglycoside / Polyion Complex / siRNA / Neomycin / cancer / Nucleic Acid / RNA-binding

Outline of Annual Research Achievements

The purpose of the current research is to construct PIC micelles, 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 acid type biomolecules for combination-therapy against cancer. In terms of polymer synthesis, we have prepared two novel block copolymers conjugated with azide functionalized neomycin through Huisgen 1,3-Dipolar Cycloaddition between the azide function of neomycin and alkyne function of polymer. Alkyne functional group was introduced in poly(ethylene glycol)-b-poly(β-benzyl-aspartamide) polymers via aminolysis reaction utilizing an amine and alkyne containing bi-functional linker. In one polymer, we used single arm polyethylene glycol (PEG) having molecular weight of 12Kilo Dalton (KD) and with 20 repeating units of poly amino acid segments; this polymer and nucleic acid complex, self assembled in a PIC micelle type structure. In another polymer we utilized dual armed PEG with each arm having molecular weight of 40 KD and with only 6 repeating units of poly amino acid segments, this polymer was prepared to form Unit PIC type particles with a single polymer and single siRNA.

Research Products

• [Journal Article] Nanomaterial-Enabled Cancer Therapy (2017)
  • Author(s): Sabina Quader, Kazunori Kataoka
  • Journal Title: Molecular Therapy Volume: 25 Pages: 1501-1513
  • DOI: https://doi.org/10.1016/j.ymthe.2017.04.026
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Proteasome Inhibitor-Loaded Micelles Enhance Antitumor Activity Through Macrophage Reprogramming by NF-κB Inhibition (2017)
  • Author(s): Wu H, Tao A, Martin JD, Quader S, Liu X, Takahashi K, Hespel L, Miura Y, Hayakawa Y, Irimura T, Cabral H, Kataoka K.
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 106 Pages: 2438-2446
  • DOI: 10.1016/j.xphs.2017.03.031.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Effective treatment of drug resistant recurrent breast tumors harboring cancer stem-like cells by staurosporine/epirubicin co-loaded polymeric micelles (2017)
  • Author(s): Zhang J, Kinoh H, Hespel L, Liu X, Quader S, Martin J, Chida T, Cabral H, Kataoka K
  • Journal Title: Journal of Controlled Release Volume: 264 Pages: 127-135
  • DOI: 10.1016/j.jconrel.2017.08.025.
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] cRGD peptide-installed epirubicin-loaded polymeric micelles for effective targeted therapy against brain tumors. (2017)
  • Author(s): Quader S, Liu X, Chen Y, Mi P, Chida T, Ishii T, Miura Y, Nishiyama N, Cabral H, Kataoka K
  • Journal Title: Journal of Controlled Release Volume: 258 Pages: 56-66
  • DOI: 10.1016/j.jconrel.2017.04.033.
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Targeting cancer using stimuli-sensitive polymeric micelle (2018)
  • Author(s): Sabina Quader, Kazunori Kataoka
  • Organizer: International Symposium on Biorelated Polymers: 255th ACS National Meeting.
  • 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
  • Int'l Joint Research
• [Presentation] Nanocarrier system for cancer therapy (2017)
  • Author(s): Sabina Quader
  • Organizer: Summer School Nanosciences, Fundamental and Applications Emphasizing in Nanomedicine. Institute of Technology Bandung, Indonesia.
  • 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
  • Int'l Joint Research