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Design and evaluation of the theranostic potential of tumor-targeted polymeric micelle of zinc protoporphyrin

Research Project

Project/Area Number 25430162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor therapeutics
Research InstitutionSojo University

Principal Investigator

FANG Jun  崇城大学, 薬学部, 准教授 (20412736)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Hideaki  崇城大学, 薬学部, 助教 (30435151)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsドラッグデリバリー / PDT / 亜鉛プロトポルフィリン / 腫瘍イメージング / プロトポルフィリン / Tumor imaging
Outline of Final Research Achievements

In this study, by using different biocompatible polymer (SMA, HA, HPMA), we prepared different polymeric conjugated ZnPP, and investigated their physiochemical characteristics, in vivo pharmacokinetics as well as antitumor activities. The results showed, 1) SMA conjugated ZnPP showed much better circulating stability and tumor accumulation than previously reported SMA-ZnPP micelle using noncovalent bond; 2) HA-ZnPP exhibited tumor-selective accumulation, more important its intracellular uptake was active in tumor cells highly expressed CD44, leading to high cytotoxicity and antitumor effect; 3) among these ZnPP micelles, HPMA-ZnPP exhibited the best tumor accumulation, resulting in clear tumor imaging and remarkable tumor suppression upon light irradiation in different solid tumor models including carcinogen-induced tumor models. These findings suggest the potential of ZnPP micelles for cancer treatment, especially the potential of HMPA-ZnPP as a cancer theranostic PDT/PDD agent.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (20 results)

All 2016 2015 2014 2013

All Journal Article (12 results) (of which Peer Reviewed: 11 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.2016

    • Author(s)
      Fang J, Tsukigawa K, Liao L, Yin H, Eguchi K, Maeda H.
    • Journal Title

      J Drug Target.

      Volume: 24 Issue: 5 Pages: 399-407

    • DOI

      10.3109/1061186x.2015.1077851

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A Retrospective 30 Years After Discovery of the EPR Effect of Solid Tumors: Next-Generation Chemotherapeutics and Photodynamic-therapy-Problems, Solutions, Prospects.2016

    • Author(s)
      Maeda H, Tsukigawa K, Fang J.
    • Journal Title

      Microcirculation.

      Volume: 23 Issue: 3 Pages: 173-182

    • DOI

      10.1111/micc.12228

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced permeability and retention effect based nanomedicine, a solution for cancer2015

    • Author(s)
      Fang J.
    • Journal Title

      World J Pharmcology.

      Volume: 4 Issue: 2 Pages: 168-171

    • DOI

      10.5497/wjp.v4.i2.168

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of different chemical bonds in pegylation of zinc protoporphyrin that affects drug release, intracellular uptake, and therapeutic effect in the tumor.2015

    • Author(s)
      Tsukigawa K, Nakamura H, Fang J, Otagiri M, Maeda H
    • Journal Title

      Eur J Pharm Biopharm.

      Volume: 89 Pages: 259-270

    • DOI

      10.1016/j.ejpb.2014.12.016

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photodynamic therapy and imaging based on tumor-targeted nanoprobe, polymer-conjugated zinc protoporphyrin.2015

    • Author(s)
      Fang J, Liao L, Yin H, Nakamura H, Subr V, Ulbrich K, Maeda H.
    • Journal Title

      Future Sci. OA.

      Volume: 1 Issue: 3

    • DOI

      10.4155/fso.15.2

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enhanced Bacterial Tumor Delivery by Modulating the EPR Effect and Therapeutic Potential of Lactobacillus casei.2014

    • Author(s)
      Fang J, Liao L, Yin H, Nakamura H, Shin T, Maeda H.
    • Journal Title

      J Pharm Sci.

      Volume: 103 Issue: 10 Pages: 3235-43

    • DOI

      10.1002/jps.24083

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Styrene-maleic acid copolymer-encapsulated CORM2, a water-soluble carbon monoxide (CO) donor with a constant CO-releasing property, exhibits therapeutic potential for inflammatory bowel disease.2014

    • Author(s)
      Yin H, Fang J, Liao L, Nakamura H, Maeda H.
    • Journal Title

      J Control Release.

      Volume: 187 Pages: 14-21

    • DOI

      10.1016/j.jconrel.2014.05.018

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Upregulation of heme oxygenase-1 in colorectal cancer patients with increased circulation carbon monoxide levels, potentially affects chemotherapeutic sensitivity.2014

    • Author(s)
      Yin H, Fang J, Liao L, Maeda H, Su Q.
    • Journal Title

      BMC Cancer.

      Volume: 14 Issue: 1 Pages: 436-436

    • DOI

      10.1186/1471-2407-14-436

    • Related Report
      2014 Research-status Report
    • Open Access
  • [Journal Article] Two step mechanisms of tumor selective delivery of N-(2-hydroxypropyl)methacrylamide copolymer conjugated with pirarubicin via an acid-cleavable linkage.2014

    • Author(s)
      Nakamura H, Etrych T, Chytil P, Ohkubo M, Fang J, Ulbrich K, Maeda H.
    • Journal Title

      J Control Release

      Volume: 174C Pages: 81-87

    • DOI

      10.1016/j.jconrel.2013.11.011

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protection from inflammatory bowel disease and colitis-associated carcinogenesis with 4-vinyl-2,6-dimethoxyphenol (canolol) involve suppression of oxidative stress and inflammatory cytokines.2013

    • Author(s)
      Fang J, Seki T, Tsukamoto T, Qin H, Yin H, Liao L, Nakamura H, Maeda H.
    • Journal Title

      Carcinogenesis

      Volume: 34 Issue: 12 Pages: 2833-2841

    • DOI

      10.1093/carcin/bgt309

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Micelles of zinc protoporphyrin conjugated to N-(2-hydroxypropyl)2013

    • Author(s)
      Nakamura H, Liao L, Hitaka Y, Tsukigawa K, Subr V, Fang J, Ulbrich K, Maeda H.
    • Journal Title

      J Control Release

      Volume: 165 Issue: 3 Pages: 191-198

    • DOI

      10.1016/j.jconrel.2012.11.017

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo.2013

    • Author(s)
      Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors
    • Journal Title

      Adv Drug Deliv Rev.

      Volume: 65 Issue: 1 Pages: 71-79

    • DOI

      10.1016/j.addr.2012.10.002

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Photodynamic therapy and imaging based on tumor-targeted nanoprobe, pHPMA-conjugated zinc protoporphyrin, and its augmentation.2015

    • Author(s)
      Jun Fang, Hideaki Nakamura, Vladmimir Subr, Karel Ulbrich, Hiroshi Maeda.
    • Organizer
      Symposium of 30 Years Anniversary of the EPR Effect: Revolution in Tumor Drug Delivery using Nanomedicine.
    • Place of Presentation
      Changchun, P.R.China
    • Year and Date
      2015-11-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Photodynamic therapy and imaging based on tumor-targeted nanoprobe, pHPMA-conjugated zinc protoporphyrin, and its augmentation2015

    • Author(s)
      Jun Fang, Hideaki Nakamura, Vladmimir Subr, Karel Ulbrich, Hiroshi Maeda.
    • Organizer
      International conference on Clinical Sciences and Drug Discovery (CSDD-2015)
    • Place of Presentation
      Baltimore, MA, USA
    • Year and Date
      2015-11-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腫瘍標的型亜鉛プロトポルフィリンP-HPMAミセルを用いる癌光化学治療とイメージング2015

    • Author(s)
      方 軍、寥 龍、中村 秀明、Vladimir Subr、Karel Ulbrich、前田 浩
    • Organizer
      第31回日本DDS学会
    • Place of Presentation
      京王プラザホテル(東京都、新宿区)
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] Upregulation of HO-1 in colorectal cancer with increased circulation CO levels, potentially affects chemosensitivity.2014

    • Author(s)
      Jun Fang, Hongzhuan Yin, Long Liao, Hiroshi Maeda.
    • Organizer
      73th Annual Meeting of the Japanese Cancer Association.
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Micelles of CO releasing molecules encapsulated by styrene-maleic acid copolymer, exhibit therapeutic potential for inflammatory bowel disease with disease-targeting property by EPR effect.2014

    • Author(s)
      Jun Fang, Haibo Qin, Hongzhuan Yin, Hideaki Nakamura, Hiroshi Maeda.
    • Organizer
      10th International Symposium on Polymer Therapeutics: From laboratory to Clinical Practice.
    • Place of Presentation
      Valencia (Spain)
    • Year and Date
      2014-05-19 – 2014-05-21
    • Related Report
      2014 Research-status Report
  • [Presentation] Preparation of a water soluble carbon monoxide donor, SMA-CORM2 micelles, and therapeutic potential for inflammatory bowel diseases.2014

    • Author(s)
      Jun Fang, Haibo Qin, Hongzhuan Yin, Hideaki Nakamura, Hiroshi Maeda.
    • Organizer
      The 40th Annual Meeting and Exposition of the Controlled Release Society
    • Place of Presentation
      Hawaii Convention Center, Honolulu, Hawaii, U.S.A.
    • Related Report
      2013 Research-status Report
  • [Presentation] 水溶性DDS型COドナーSMAミセルの作製とその抗炎症作用2013

    • Author(s)
      方 軍、殷 紅専、寥 龍、中村 秀明、前田 浩
    • Organizer
      第29回日本DDS学会
    • Place of Presentation
      京都府、京都市、京都テルサ
    • Related Report
      2013 Research-status Report
  • [Presentation] Evaluation of the targeted photodynamic therapeutic effect of HPMA-zinc protoporphyrin micelle in different tumor models.2013

    • Author(s)
      Jun Fang, Long Liao, Hongzhuan Yin, Hideaki Nakamura, Hiroshi Maeda.
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      神奈川県、横浜市、パシフィコ横浜
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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