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

Research Project

Project/Area Number 18K18393
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionKawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine

Principal Investigator

Dirisala Anjaneyulu  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
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsRES blockade / PEG coating to liver / Two-arm-PEG-peptide / Bile clearance / Retargeting nanomedicine / Reticuloendothelium / Sinusoidal wall / Two-arm-PEG-OligoLysine / Liver blockade / Single arm PEG-OLys / Double arm PEG-OLys / PEG-oligo(amino acid)
Outline of Final Research Achievements

A single biggest issue of systemically injected nanomedicines is nonspecific elimination by the liver sinusoidal wall cells, which substantially decrease the delivery efficiency at diseased sites. We addressed this issue by stealth coating of liver sinusoidal wall using single- or two-armed poly(ethylene glycol) (PEG)-conjugated oligo(l-lysine)(OligoLys). PEG-OligoLys selectively coated to the liver sinusoidal wall, leaving the other tissue endothelium uncoated and, thus, accessible to the nanomedicine delivery. Interestingly, 2-arm-PEG-OligoLys uncoated the sinusoidal wall within hours and cleared to the bile, while 1-arm-PEG-OligoLys persisted at the wall. Such transient and selective stealth coating of sinusoidal wall by two-arm-PEG-OligoLys was effective in preventing the sinusoidal clearance of nonviral and viral gene vectors, representatives of synthetically-engineered and nature-derived nanomedicines, respectively, thereby boosting their gene transduction at the diseased sites.

Academic Significance and Societal Importance of the Research Achievements

Our transient and selective stealth coating strategy is expected to (i) improve the efficacy of gene therapy drugs, (ii) reduce the dose required to obtain therapeutic outcomes, and (iii) decrease dose-related toxicities, which ultimately lead to the reduction of the medical cost of nanomedicines.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 3 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 3 results)

  • [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 efficiency2021

    • Author(s)
      Yoshinaga Naoto、Uchida Satoshi、Dirisala Anjaneyulu、Naito Mitsuru、Osada Kensuke、Cabral Horacio、Kataoka Kazunori
    • Journal Title

      Journal of Controlled Release

      Volume: 330 Pages: 317-328

    • DOI

      10.1016/j.jconrel.2020.12.033

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Co-encapsulation of Cas9 mRNA and guide RNA in polyplex micelles enables genome editing in mouse brain2021

    • Author(s)
      S. Abbasi, S. Uchida, K. Toh, T.A. Tockary, A. Dirisala, K. Hayashi, S. Fukushima, K. Kataoka
    • Journal Title

      J. Control. Release

      Volume: 332 Pages: 260-268

    • DOI

      10.1016/j.jconrel.2021.02.026

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines2020

    • Author(s)
      Dirisala Anjaneyulu、Uchida Satoshi、Toh Kazuko、Li Junjie、Osawa Shigehito、Tockary Theofilus A.、Liu Xueying、Abbasi Saed、Hayashi Kotaro、Mochida Yuki、Fukushima Shigeto、Kinoh Hiroaki、Osada Kensuke、Kataoka Kazunori
    • Journal Title

      Science Advances

      Volume: 6 Issue: 26

    • DOI

      10.1126/sciadv.abb8133

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dual-Sensitive Nanomicelles Enhancing Systemic Delivery of Therapeutically Active Antibodies Specifically into the Brain2020

    • 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*, and Kazunori Kataoka
    • Journal Title

      ACS Nano

      Volume: - Issue: 6 Pages: 6729-6742

    • DOI

      10.1021/acsnano.9b09991

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Targeting nanoparticles to the brain by exploiting the blood-brain barrier impermeability to selectively label the brain endothelium2020

    • Author(s)
      Daniel Gonzalez-Carter, Xueying Liu, Theofilus A Tockary, Anjaneyulu Dirisala , Kazuko Toh , Yasutaka Anraku , Kazunori Kataoka
    • Journal Title

      Proc Natl Acad Sci U S A .

      Volume: 117 (32) Issue: 32 Pages: 19141-19150

    • DOI

      10.1073/pnas.2002016117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Precise tuning of disulfide crosslinking in mRNA polyplex micelles for optimizing extracellular and intracellular nuclease tolerability.2019

    • Author(s)
      A. Dirisala, S. Uchida, T. A. Tockary, N. Yoshinaga, J. Li, S. Osawa, L. Gorantla, S. Fukushima, K. Osada, K. Kataoka
    • Journal Title

      J. Drug Target.

      Volume: 印刷中 Issue: 5-6 Pages: 670-680

    • DOI

      10.1080/1061186x.2018.1550646

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Single-stranded DNA-packaged polyplex micelle as adeno-associated-virus-inspired compact vector to systemically target stroma-rich pancreatic cancer.2019

    • Author(s)
      T. A. Tockary, W. Foo, A. Dirisala, Q. Chen, S. Uchida, S. Osawa, Y. Mochida, X. Liu, H. Kinoh, H. Cabral, K. Osada, K. Kataoka
    • Journal Title

      ACS Nano

      Volume: 13 Issue: 11 Pages: 12732-12742

    • DOI

      10.1021/acsnano.9b04676

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Precise tuning of disulphide crosslinking in mRNA polyplex micelles for optimising extracellular and intracellular nuclease tolerability.2019

    • Author(s)
      Dirisala A, Uchida S, Tockary TA, Yoshinaga N, Li J, Osawa S, Gorantla L, Fukushima S, Osada K, Kataoka K.
    • Journal Title

      J Drug Target

      Volume: 27

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Liver sinusoidal blockade by poly(ethylene glycol)-oligo(amino acid) block copolymers for tuning pharmacokinetics of NanoMedicine2019

    • Author(s)
      Anjaneyulu Dirisala, Satoshi Uchida, Kazuko Toh, Shigehito Osawa, Kotaro Hayashi, Kazunori Kataoka
    • Organizer
      2019 International Symposium on Nanotechnology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Liver sinusoidal blockade by poly(ethylene glycol)-oligo(amino acid) block copolymers for tuning pharmacokinetics of NanoMedicine2019

    • Author(s)
      Anjaneyulu Dirisala, Satoshi Uchida, Kazuko Toh, Shigehito Osawa, Kotaro Hayashi, Kazunori Kataoka
    • Organizer
      The 12th Annual Symposium on Nanotechnology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of poly(ethylene glycol) molecular weight for overcoming liver sinusoidal barrier towards prolonged circulation activity of polyplex micelles2018

    • Author(s)
      Dirisala Anjaneyulu, Kensuke Osada, Kazuko Toh, Theofilus A. Tockary, Satoshi Uchida, Horacio Cabral, Kazunori Kataoka
    • Organizer
      The 12th SPSJ International Polymer Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] Composition controlling pharmacokinetics in the body2020

    • Inventor(s)
      Kazunori Kataoka et al
    • Industrial Property Rights Holder
      Kazunori Kataoka et al
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 体内における薬物動態を制御する組成物2019

    • Inventor(s)
      片岡 一則 et al.,
    • Industrial Property Rights Holder
      片岡 一則 et al.,
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 体内における薬物動態を制御する組成物2019

    • Inventor(s)
      Kataoka K, et al.,
    • Industrial Property Rights Holder
      川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report
    • Overseas

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Published: 2018-04-23   Modified: 2022-01-27  

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