• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Augmentation of EPR effect and therapeutic effect of nanomedicine by improving tumor microenvironment

Research Project

Project/Area Number 16K08217
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionSojo University

Principal Investigator

FANG Jun  崇城大学, 薬学部, 准教授 (20412736)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsEPR効果 / DDS / 腫瘍ターゲティング / ナノメディシン / 一酸化窒素 / 一酸化炭素 / 腫瘍微小環境 / ニトログリセリン / アルギニン / ヒドロキシウレア / ドラッグデリバリー / 腫瘍
Outline of Final Research Achievements

In this study, we have investigated approaches to augment EPR effect/tumor drug delivery of macromolecular nanomedicines, by improving tumor blood flow. For this aim, we focused on vascular mediators involved in EPR effect, i.e., nitric oxide (NO) and carbon monoxide (CO), and examined their potentials to enhance the delivery of nanomedicines into tumor, by using NO/CO generators. The NO/CO generators induced the generation of NO/CO more selectively in tumor, which in turn resulted in the improvement of tumor blood flow and increase of nano-drugs in tumor (EPR effect). Consequently, by combining with these NO/CO generators, the anticancer effect of nanomedicines were significantly elevated which were verified in different solid tumor models including carcinogen-induced cancers. These findings strongly suggested the potentials of these NO/CO generators as EPR enhancers to improve the therapeutic effects of nanomedicines.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、腫瘍血流の改善による副作用の少ないEPR効果/高分子抗がん治療の増強法を確立できると考えられる。その結果、高分子抗がん剤の腫瘍内デリバリーが数倍から数十倍増加でき、より効率の良い、これまで以上優れた抗がん治療効果が得られる。つまり、本研究の成果はがんの効率的な治療へとつながり、医療費の削減ならびにがん患者のQOLを上げることに寄与するものと強く期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (16 results)

All 2018 2017 2016 Other

All Int'l Joint Research (4 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 6 results,  Invited: 3 results)

  • [Int'l Joint Research] Inst. Macromolecular Chemistry, AS CR(チェコ)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Inst. Macromolecular Chemistry, AS CR(チェコ)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Inst. Macromolecular Chemistry, AS CR(チェコ)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Augmentation of the enhanced permeability and retention effect with nitric oxide-generating agents improves the therapeutic effects of nanomedicines.2018

    • Author(s)
      Islam, W., Fang, J., Imamura, T., Etrych, T., Subr, V., Ulbrich K., & Maeda, H.
    • Journal Title

      Mol. Cancer Therap.

      Volume: 17 Issue: 12 Pages: 2643-2653

    • DOI

      10.1158/1535-7163.mct-18-0696

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] N-(2-hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging.2018

    • Author(s)
      Fang J, Subr V, Islam W, Hackbarth S, Islam R, Etrych T, Ulbrich K, Maeda H.
    • Journal Title

      Eur J Pharm Biopharm.

      Volume: 130 Pages: 165-176

    • DOI

      10.1016/j.ejpb.2018.06.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] がんセラノスティックスを目指したHPMAポリマー結合型Pyropheophorbide-aの開発2018

    • Author(s)
      方 軍、Vladimr Subr、Waliul Md. Islam、Steffen Hackbarth、Tomas Etrych、Karel Ulbrich、前田 浩
    • Organizer
      第34回日本DDS学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] N-(2-Hydroxypropyl)methacrylamide polymer conjugated pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging.2018

    • Author(s)
      Jun Fang, Vladimr Subr, Waliul Islam, Steffen Hackbarth, Tomáš Etrych, Karel Ulbrich, Hiroshi Maeda.
    • Organizer
      International Conference on Medicinal Chemistry & Drug Design.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Polymeric pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging.2018

    • Author(s)
      Jun Fang, Waliul Islam, Hiroshi Maeda.
    • Organizer
      77th Annual Meeting of the Japanese Cancer Association.
    • Related Report
      2018 Annual Research Report
  • [Presentation] Augmentation of tumor-targeted PDT by using nitric oxide generating agents.2017

    • Author(s)
      Jun Fang
    • Organizer
      International symposium of polymer therapeutics focusing the EPR effect and its Future Development
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Characterization and evaluation of photodynamic effect of HPMA copolymer based nanoprobes.2017

    • Author(s)
      Jun Fang, Waliul Islam, Vladmimir Subr, Karel Ulbrich, Hiroshi Maeda
    • Organizer
      Trilateral, Japan-Israel-Czech Republic, International Symposium of Polymer Therapeutics Focusing on the Targeted Nanomedicines
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 一酸化窒素産生薬を用いるEPR効果増強法の検討2017

    • Author(s)
      方軍、Waliul Islam、Tomas Etrych、Petr Chytil、Karel Ulbrich、前田浩
    • Organizer
      第33回日本DDS学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Nitric oxide generating agents enhance tumor-targeted photodynamic therapy by modulating tumor microenvironment2017

    • Author(s)
      Jun Fang, Waliul Md. Islam, Hiroshi Maeda
    • Organizer
      第76回日本癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Augmentation of tumor-targeted photodynamic therapy and imaging by modulating tumor microenvironment using nitric oxide generating agents.2017

    • Author(s)
      Jun Fang, Waliul Md. Islam, Vladmimir Subr, Tomas Etrych, Karel Ulbrich, Hiroshi Maeda.
    • Organizer
      The 44th Annual Meeting and Exposition of the Controlled Release Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photodynamic therapy and imaging based on tumor-targeted nanoprobe, pHPMA-conjugated zinc protoporphyrin, and its augmentation.2016

    • Author(s)
      Jun Fang, Hideaki Nakamura, Vladmimir Subr, Karel Ulbrich, Hiroshi Maeda.
    • Organizer
      International Conference on Pharmaceutical Chemistry
    • Place of Presentation
      Frankfurt, Germany
    • Year and Date
      2016-09-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Photodynamic therapy and imaging based on tumor-targeted nanoprobe, pHPMA-conjugated zinc protoporphyrin, and its augmentation.2016

    • Author(s)
      Jun Fang, Hideaki Nakamura, Vladmimir Subr, Karel Ulbrich, Hiroshi Maeda.
    • Organizer
      11th International Symposium on Polymers Therapeutics From Laboratory to Clinical Practice.
    • Place of Presentation
      The Centro de Investigacion Principe Felipe (CIPF), Valencia, Spain
    • Year and Date
      2016-05-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi