Reticuloendothelial system blockade by PEG-oligo(amino acid) block copolymers: A strategy for functional tuning of nanomedicine pharmacokinetics

2020 Fiscal Year Annual Research Report

• Project/Area Number: 18K18393
• Research Institution: Kawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine
• Principal Investigator: ディリサラ アンジャネユル 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, 研究員 (70794353)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: RES blockade / PEG coating to liver / Two-arm-PEG-peptide / Bile clearance / Retargeting nanomedicine

Outline of Annual Research Achievements

A single issue of systemically injected nanomedicines is nonspecific elimination by liver scavenger wall, which substantially decreasing the delivery efficiency at target tissues. We addressed this issue by in situ stealth coating of scavenger wall using 1- or 2-armed poly(ethylene glycol) (PEG)-oligo(L-lysine). PEG-OligoLys selectively coat the scavenger wall, leaving other tissue endothelium uncoated, thus, accessible to nanomedicine extravasation. Interestingly, 2-arm-PEG-OligoLys was cleared from wall to bile within hours, while 1-arm-PEG-OligoLys persisted at the wall. Such transient and selective stealth coating by 2-arm-PEG-OligoLys effectively suppressed the elimination of nonviral and viral gene vectors by scavenger wall, thereby boosting their gene transduction at target organs.

Research Products

• [Journal Article] mRNA loading into ATP-responsive polyplex micelles with optimal density of phenylboronate ester crosslinking to balance robustness in the biological milieu and intracellular translational efficiency (2021)
  • Author(s): Naoto Yoshinaga, Satoshi Uchida, Anjaneyulu Dirisala, Mitsuru Naito, Kensuke Osada, Horacio Cabral, Kazunori Kataoka
  • Journal Title: Journal of Controlled Release Volume: 330 Pages: 317-328
  • DOI: 10.1016/j.jconrel.2020.12.033
  • Int'l Joint Research
• [Journal Article] Co-encapsulation of Cas9 mRNA and guide RNA in polyplex micelles enables genome editing in mouse brain (2021)
  • Author(s): Saed Abbasi, Satoshi Uchida, Kazuko Toh, Theofilus A Tockary, Anjaneyulu Dirisala, Kotaro Hayashi, Shigeto Fukushima, Kazunori Kataoka
  • Journal Title: Journal of Controlled Release Volume: 332 Pages: 260-268
  • DOI: 10.1016/j.jconrel.2021.02.026
  • Int'l Joint Research
• [Journal Article] Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines (2020)
  • Author(s): Anjaneyulu Dirisala, Satoshi Uchida, Kazuko Toh, Junjie Li, Shigehito Osawa, Theofilus A Tockary, Xueying Liu, Saed Abbasi, Kotaro Hayashi, Yuki Mochida, Shigeto Fukushima, Hiroaki Kinoh, Kensuke Osada, Kazunori Kataoka
  • Journal Title: Science Advances Volume: 6 (26) Pages: eabb8133
  • DOI: 10.1126/sciadv.abb8133
  • Open Access / Int'l Joint Research
• [Journal Article] Dual-sensitive nanomicelles enhancing systemic delivery of therapeutically active antibodies specifically into the brain (2020)
  • Author(s): Jinbing Xie, Daniel Gonzalez-Carter, Theofilus A Tockary, Noriko Nakamura, Yonger Xue, Makoto Nakakido, Hiroki Akiba, Anjaneyulu Dirisala, Xueying Liu, Kazuko Toh, Tao Yang, Zengtao Wang, Shigeto Fukushima, Junjie Li, Sabina Quader, Kouhei Tsumoto, Takanori Yokota, Yasutaka Anraku, Kazunori Kataoka
  • Journal Title: ACS nano Volume: 14 (6) Pages: 6729-6742
  • DOI: 10.1021/acsnano.9b09991
  • Int'l Joint Research
• [Journal Article] Targeting nanoparticles to the brain by exploiting the blood-brain barrier impermeability to selectively label the brain endothelium (2020)
  • Author(s): Daniel Gonzalez-Carter, Xueying Liu, Theofilus A. Tockary, Anjaneyulu Dirisala, Kazuko Toh, Yasutaka Anraku, Kazunori Kataoka
  • Journal Title: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Volume: 117 (32) Pages: 19141-19150
  • DOI: 10.1073/pnas.2002016117
• [Patent(Industrial Property Rights)] Composition controlling pharmacokinetics in the body (2020)
  • Inventor(s): Kazunori Kataoka et al
  • Industrial Property Rights Holder: Kazunori Kataoka et al
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: US20210038634A1
  • Overseas