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Developing brain-penetrating anti-inflammatory nano-medicines to treat neurodegenerative diseases

Research Project

Project/Area Number 18K14100
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 28040:Nanobioscience-related
Research InstitutionKawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine

Principal Investigator

Gonzalez Carter Daniel Angel  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 (80800903)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsNanoparticles / Brain / Blood-brain barrier / Glucose / Alzheimer's / Brain targeting / Brain vasculature label / mRNA delivery / Labelled proteins / BBB penetration / Nanomicelle / Protein loading / CD200 protein / Brain inflammation / Polymeric nano-micelles / Brain penetration / Anti-inflammation / Alzheimer's disease
Outline of Final Research Achievements

We created a nano-carrier system capable of delivering therapeutic payloads specifically into the brain. We designed nanoparticles decorated with glucose (G-NP) capable of encapsulating therapeutic antibodies. By modulating blood-glucose levels, we were able to induce movement of the glucose transporter Glut-1 specifically across brain endothelial cells (BEC). Hence, the G-NP bound to the Glut-1 were transported across BEC to release their therapeutic cargo specifically in the brain. We demonstrated the therapeutic potential of this strategy by delivering antibodies capable of preventing aggregation of amyloid-beta, a key pathological mechanism in Alzheimer's disease.

We also developed a new brain-targeting strategy which exploits the impermeability of the blood-brain barrer to selectively label BEC. This strategy has the benefit that it does not modify the physiology of the organism, therefore has great potential for clinical translation.

Academic Significance and Societal Importance of the Research Achievements

Treating neurodegenerative diseases is severely limited by the poor entry of therapies into the brain. We have developed two different strategies capable of delivering nanoparticles specifically to the brain, thereby paving the way to deliver a wide-range of therapies into the brain.

Report

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

    (9 results)

All 2021 2020 2019 2018

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results) (of which Invited: 4 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [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] 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
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Targeting Nanoparticles to the Brain by Exploiting the BBB impermeability to Label the Brain Endothelium2020

    • Author(s)
      Daniel Gonzalez Carter
    • Organizer
      Vancouver Nanomedicine Day
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Targeting nanoparticles to the brain by exploiting the blood-brain barrier impermeability to selectively label the brain endothelium2020

    • Author(s)
      Gonzalez-Carter, Daniel
    • Organizer
      Nanobio2020 (post-poned due to Coronavirus)
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Delivering anti-inflammatory therapies into the brain through brain-targeted polymeric nano-vehicles2019

    • Author(s)
      Gonzalez-Carter, Daniel
    • Organizer
      12th International Symposium on Nanobiotechnology
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Developing Cell-targeted, Brain-penetrating Polymeric Nano-micelles to Treat Neurodegenerative diseases2018

    • Author(s)
      Gonzalez-Carter, Daniel
    • Organizer
      11th European and Global Summit for Clinical Nanomedicine (CLINAM)
    • Related Report
      2018 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] A METHOD OF ADMIINISTERING A NANOPARTICLE2021

    • Inventor(s)
      片岡 一則、ゴンザレス カーター ダニエル
    • Industrial Property Rights Holder
      公益財団法人川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] A METHOD OF ADMIINISTERING A NANOPARTICLE2020

    • Inventor(s)
      片岡 一則、ゴンザレス カーター ダニエル
    • Industrial Property Rights Holder
      公益財団法人川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-055478
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] Japan patent office2020

    • Inventor(s)
      Gonzalez Carter Daniel
    • Industrial Property Rights Holder
      Gonzalez Carter Daniel
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report

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

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