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Development of Reversible Double-Layer Polymer Modification Technology to Break the Safety/Efficacy Trade-Off of Delivering Enzyme

Research Project

Project/Area Number 23K28429
Project/Area Number (Other) 23H03740 (2023)
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeMulti-year Fund (2024)
Single-year Grants (2023)
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionKyushu University

Principal Investigator

LI JUNJIE  九州大学, 先導物質化学研究所, 准教授 (80869892)

Co-Investigator(Kenkyū-buntansha) 田中 賢  九州大学, 先導物質化学研究所, 教授 (00322850)
小林 慎吾  九州大学, 先導物質化学研究所, 特任准教授 (70625110)
Project Period (FY) 2023-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2025: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2024: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2023: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Keywordsenzyme delivery / polymer / oxidation therapy / nanoreactor / polymer-enzyme conjugate / safety/efficacy / stimuli-responsiveness / nano-bio interaction
Outline of Research at the Start

This polymer delivery system can synchronize long circulation in blood, precise clearance and degradation by macrophage, and enzyme activation in tumor. The key points are to control hydrophilic-hydrophobic balance and number of modified polymers to enable (i) long blood circulation and macrophage-tropism together and (ii) degradation of enzyme before activation in macrophage.

Outline of Annual Research Achievements

This proposal aims to develop a simple delivery system for enzyme therapy. This polymer delivery system can synchronize long circulation in blood, precise clearance and degradation by macrophage, and enzyme activation in tumor. Some polymers have been prepared for enzyme delivery. We have tried to encapsulate the enzyme (such as glucose oxidase) and evaluated the cytotoxicity. We have performed some preliminary experiments for in vivo blood circulation and toxicity.

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

The project progress smoothly.

Strategy for Future Research Activity

We will perform the detailed cell experiments (such as cytotoxicity) and in vivo animal experiments (such as blood circulation, biodistribution, safety, and antitumor effect).

Report

(1 results)
  • 2023 Annual Research Report
  • Research Products

    (5 results)

All 2023

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

  • [Journal Article] Stealth and pseudo-stealth nanocarriers2023

    • Author(s)
      Wen Panyue、Ke Wendong、Dirisala Anjaneyulu、Toh Kazuko、Tanaka Masaru、Li Junjie
    • Journal Title

      Advanced Drug Delivery Reviews

      Volume: 198 Pages: 114895-114895

    • DOI

      10.1016/j.addr.2023.114895

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Controlling the biodistribution and clearance of nanomedicines2023

    • Author(s)
      Cabral Horacio、Li Junjie、Miyata Kanjiro、Kataoka Kazunori
    • Journal Title

      Nature Reviews Bioengineering

      Volume: 2 Issue: 3 Pages: 214-232

    • DOI

      10.1038/s44222-023-00138-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Presentation] The cooperative intermolecular ion-pair network sheath enables super-stealth effect2023

    • Author(s)
      Junjie Li
    • Organizer
      第45回日本バイオマテリアル学会大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Cooperative intermolecular ion-pair network sheath enables super-stealth effect2023

    • Author(s)
      Junjie Li
    • Organizer
      第52回医用高分子シンポジウム
    • Related Report
      2023 Annual Research Report
  • [Presentation] Stimuli-responsive polymersomes-based activable therapeutic nanoreactors for tumor-specific cancer therapy2023

    • Author(s)
      Junjie Li
    • Organizer
      Cell Symposia
    • Related Report
      2023 Annual Research Report

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Published: 2023-04-18   Modified: 2024-12-25  

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