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Augmentation of EPR effect and therapeutic effect of nanomedicine by inhibiting off-targeting delivery

Research Project

Project/Area Number 19K07743
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionSojo University

Principal Investigator

Fang Jun  崇城大学, 薬学部, 准教授 (20412736)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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)
KeywordsEPR効果 / ナノメディシン / off-targetデリバリー / イントラリピッド / 腫瘍血流 / EPR effect / Tumor targeting / Intralipid / RES / Off-target delivery / off-target delivery / オフターゲットデリバリー / 効果増強
Outline of Research at the Start

本研究では、腫瘍以外のoff-target deliveryの抑制を目指すことで、ナノメディシンの血中滞留性・腫瘍集積性(EPR効果)の増強およびそれによるナノメディシンの抗がん治療効果増強戦略の探索を目的とする。網内系(RES)機能抑制作用を持つ臨床静注用脂肪乳剤Intralipidに注目し、高分子ナノ製剤の肝臓、脾臓への集積の減少、血中半減期の増加および腫瘍デリバリーの促進作用を検討し、その作用機序を解明する上、その臨床応用の可能性を明らかにしたい。この結果を生かすことにより、抗がんナノメディシンのoff-targetの抑制・副作用の減少とより効率のよい抗がん作用が期待される。

Outline of Final Research Achievements

In this study, we investigated the usefulness of the clinically used lipid emulsion, Intralipid, which has a function of suppressing the reticuloendothelial system, in suppressing the off-target delivery of anticancer nanomedicines. Intralipid pretreatment led to a significant reduction in liver accumulation of various anticancer nanomedicines, an increase in blood half-life, improvement in tumor blood flow, and a significant increase in tumor delivery. As a result, the combination of Intralipid and nanomedicines significantly improved the therapeutic effect of anticancer nanomedicines. These results suggest that the combination therapy of Intralipid and nanomedicines could be a new anticancer strategy with potential clinical applications.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、静脈栄養剤として臨床で広く応用されるIntralipidを用いることで、ナノメディシンのoff-targetデリバリーの抑制による副作用の少ないEPR効果の増強法を確立できると考えられます。その結果、ナノメディシンのより効率的かつこれまで以上に優れた抗がん治療効果が得られると信じています。つまり、本研究の成果はがんの効率的な治療に繋がり、医療費の削減ならびにがん患者のQOL向上に寄与するものと強く期待されています。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (25 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (10 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Int'l Joint Research] Inst. Macromol. Chem., Czech Acad. Sci.(チェコ)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Inst. Macromol. Chem., Czech Acad. Sci.(チェコ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Inst. Macromol. Chem., Czech Acad. Sci.(チェコ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Inst. Macromol. Chem., Czech Acad. Sci.(チェコ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] HPMA copolymer conjugated 5-aminolevulinic acid exhibits superior efficacy for photodynamic therapy with tumor-responsive and targeting properties.2023

    • Author(s)
      Islam R, Kotalik K, Subr V, Gao S, Zhou J-R, Yokomizo K, Etrych T, Fang J.
    • Journal Title

      Nanomedicine.

      Volume: 48 Pages: 102636-102636

    • DOI

      10.1016/j.nano.2022.102636

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Factors affecting the dynamics and heterogeneity of the EPR effect: pathophysiological and pathoanatomic features, drug formulations and physicochemical factors.2022

    • Author(s)
      Islam R, Maeda H, Fang J.
    • Journal Title

      Expert Opin Drug Deliv.

      Volume: 19(2) Issue: 2 Pages: 199-212

    • DOI

      10.1080/17425247.2021.1874916

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Expression Dynamics of Heme Oxygenase-1 in Tumor Cells and the Host Contributes to the Progression of Tumors2021

    • Author(s)
      Jun Fang, Rayhanul Islam, Shanghui Gao, Cheng Zhang, Ryotaro Kunisaki, Shogo Sakaguchi, Naoya Honda, Jian-Rong Zhou, Kazumi Yokomizo
    • Journal Title

      Journal of Personalized Medicine

      Volume: Dec; 11(12) Issue: 12 Pages: 1340-1340

    • DOI

      10.3390/jpm11121340

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Styrene Maleic Acid Copolymer-Based Micellar Formation of Temoporfin (SMA@ mTHPC) Behaves as A Nanoprobe for Tumor-Targeted Photodynamic Therapy with A Superior Safety2021

    • Author(s)
      Jun Fang, Hinata Nema, Rina Yanagibashi, Niho Yoneda, Natsumi Watanabe, Yuki Yasuda, Naoki Nuita, Jian-Rong Zhou, Kazumi Yokomizo
    • Journal Title

      Biomedicines.

      Volume: Oct 19;9(10) Issue: 10 Pages: 1493-1493

    • DOI

      10.3390/biomedicines9101493

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors.2021

    • Author(s)
      Makimoto A, Fang J, Maeda H.
    • Journal Title

      Cancers

      Volume: 13(15) Issue: 15 Pages: 3698-3698

    • DOI

      10.3390/cancers13153698

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Unraveling the role of Intralipid in suppressing off-target delivery and augmenting the therapeutic effects of anticancer nanomedicines.2021

    • Author(s)
      Islam R, Gao S, Islam W, Subr V, Zhou JR, Yokomizo K, Etrych T, Maeda H, Fang J.
    • Journal Title

      Acta Biomater.

      Volume: 126 Pages: 372-383

    • DOI

      10.1016/j.actbio.2021.03.044

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Polymer-conjugated glucosamine complexed with boric acid shows tumor-selective accumulation and simultaneous inhibition of glycolysis2021

    • Author(s)
      Islam Waliul、Matsumoto Yoshitaka、Fang Jun、Harada Ayaka、Niidome Takuro、Ono Katsuhiko、Tsutsuki Hiroyasu、Sawa Tomohiro、Imamura Takahisa、Sakurai Kazuo、Fukumitsu Nobuyoshi、Yamamoto Hirofumi、Maeda Hiroshi
    • Journal Title

      Biomaterials

      Volume: 269 Pages: 120631-120631

    • DOI

      10.1016/j.biomaterials.2020.120631

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy2021

    • Author(s)
      Gao Shanghui、Islam Rayhanul、Fang Jun
    • Journal Title

      Journal of Personalized Medicine

      Volume: 11 Issue: 2 Pages: 136-136

    • DOI

      10.3390/jpm11020136

    • Related Report
      2020 Research-status Report
  • [Journal Article] Highly effective anti-tumor nanomedicines based on HPMA copolymer conjugates with pirarubicin prepared by controlled RAFT polymerization2020

    • Author(s)
      E. Randarova, H. Nakamura, R. Islam, M. Studenovsky, Mamoru Haratake, J. Fang, P. Chytil, T. Etrych
    • Journal Title

      Acta Biomaterialia

      Volume: 106 Pages: 256-266

    • DOI

      10.1016/j.actbio.2020.02.011

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Exploiting the dynamics of the EPR effect and strategies to improve the therapeutic effects of nanomedicines by using EPR effect enhancers2020

    • Author(s)
      Fang Jun、Islam Waliul、Maeda Hiroshi
    • Journal Title

      Advanced Drug Delivery Reviews

      Volume: 157 Pages: 142-160

    • DOI

      10.1016/j.addr.2020.06.005

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] Investigating the anticancer potential of the SMA micelle encapsulating active sulfur-containing compound, Garlicin B12022

    • Author(s)
      Shanghui Gao, Jun Fang
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] HPMA polymer conjugated pyropheophorbide-a, an acidic pH responsive nanoprobe for tumor-targeted photodynamic therapy2021

    • Author(s)
      Rayhanul Islam, Hiroshi Maeda, Jun Fang
    • Organizer
      第80回日本癌学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Tumor environment-responsive nanoprobe HPMA polymer conjugated pyropheophorbide a for tumor-targeted photodynamic therapy2021

    • Author(s)
      Rayhanul Islam, Marina R. Tavares, Vladimir Subr, Tomas Etrych, Hiroshi Maeda, Jun Fang
    • Organizer
      第37回日本DDS学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Suppression of off-target delivery of nano-drugs and augmentation of therapeutic effect of nanomedicine by Intralipid2020

    • Author(s)
      Rayhanul Islam, Waliul Islam, 前田 浩, 方 軍
    • Organizer
      第36回日本DDS学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Polymer conjugated glucosamine complexed with boric acid with tumor selective accumulation and simultaneous inhibition of glycolysis2020

    • Author(s)
      Waliul Islam, 松本 孔貴, 原田 彩花, 方 軍, 澤 智裕, 新留 琢郎, 福光 延吉, 前田 浩
    • Organizer
      第36回日本DDS学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Suppression of off-target delivery of nanomedicine and augmentation of therapeutic effect of nanomedicine by Intralipid2020

    • Author(s)
      Rayhanul Islam, Waliul Islam, 前田 浩, 方 軍
    • Organizer
      第79回日本癌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Suppression of off-target delivery of nano-drugs and augmentation of therapeutic effect of nanomedicine by Intralipid2020

    • Author(s)
      Rayhanul Islam, Waliul Islam, Hiroshi Maeda, Jun Fang
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Improving therapeutic effect of nanomedicine by EPR enhancers.2019

    • Author(s)
      Jun Fang, Waliul Islam, Rayhanul Islam, Vladimir Subr, Tomas Etrych, Karel Ulbrich, Hiroshi Maeda
    • Organizer
      83th Prague Meeting on Macromolecules
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 一酸化炭素産生薬を用いるEPR効果増強法の検討2019

    • Author(s)
      方 軍, Rayhanul Islam, Waliul Islam, Vladimir Subr, 前田 浩
    • Organizer
      第35回日本DDS学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Polymeric pyropheophorbide-a, a promising tumor-targeted theranostic probe for photodynamic therapy and imaging2019

    • Author(s)
      Jun Fang, Vladimir Subr, Waliul Islam, Steffen Hackbarth, Rayhanul Islam, Takuro Niidome, Tomas Etrych, Karel Ulbrich, Hiroshi Maeda
    • Organizer
      The 46th Annual Meeting and Exposition of the Controlled Release Society
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Augmentation of EPR effect and therapeutic efficacy of nanomedicine by carbon monoxide generating agents2019

    • Author(s)
      Jun Fang, Rayhanul Islam, Waliul Islam, Hiroshi Maeda
    • Organizer
      第78回日本癌学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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