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Development of zinc protoporphyrin micelles for cancer photodymanic therapy with xenon light

Research Project

Project/Area Number 22700927
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Clinical oncology
Research InstitutionSojo University

Principal Investigator

FANG Jun  崇城大学, 薬学部, 准教授 (20412736)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywordsドラッグデリバリー / 光化学療法
Research Abstract

In this study, by comparing the physiochemical characteristics, stability as well as in vivo pharmacokinetics of different ZnPP micelles, we found that HPMA-ZnPP, with the particle size of about 80 nm, showed good stability in circulation, resulting in prolonged plasma half-life as well as tumor-selective accumulation (EPR effect). We thus selected HPMA-ZnPP for further development. In vitro studies using Hela cells exhibited a strong cytotoxicity of HPMA-ZnPP upon light irradiation. In vivo experiments showed an HPMA-ZnPP dose-dependent and irradiation dependent (intensity and duration) suppression of tumor growth. Moreover, the tumor-selective accumulation of HPMA-ZnPP was clearly detected in an in vivo imaging system. Token together, these findings strongly suggest the potential of HPMA-ZnPP as a new PDT drug for cancer, at the same time with tumor-detecting potency.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (30 results)

All 2013 2012 2011 2010

All Journal Article (8 results) (of which Peer Reviewed: 8 results) Presentation (17 results) (of which Invited: 3 results) Book (3 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [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
      2012 Annual Research Report 2012 Final Research 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
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] HSP32 (HO-1) inhibitor, copoly(styrene maleic acid)-zinc protoporphyrin IX, a water soluble micelle as anticancer agent: in vitro and in vivo anticancer effect.2012

    • Author(s)
      Fang J, Greish K, Qin H, Liao L, Nakamura H, Takeya M, Maeda H.
    • Journal Title

      Eur J

      Volume: 81 Issue: 3 Pages: 540-547

    • DOI

      10.1016/j.ejpb.2012.04.016

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] HSP32 (HO-1) inhibitor, zinc protoporphyrin IX, a water soluble micelle of copoly (styrene maleic acid) as anticancer agent : in vitro and in vivo anticancer effect2012

    • Author(s)
      Jun Fang, et al
    • Journal Title

      Eur J Pharm.Biopharm.

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents; Unique intracellular disintegration of SMA micelles.2011

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

      J Control Release

      Volume: 155 Pages: 367-375

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect.2011

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

      Adv Drug Deliv Rev

      Volume: 63 Issue: 3 Pages: 136-151

    • DOI

      10.1016/j.addr.2010.04.009

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents ; Unique intracellular disintegration of SMA micelles2011

    • Author(s)
      Hideaki Nakamura, Jun Fang, et al
    • Journal Title

      J Control Release

      Volume: 155 Issue: 3 Pages: 367-375

    • DOI

      10.1016/j.jconrel.2011.04.025

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents ; Unique intracellular disintegration of SMA micelles.2011

    • Author(s)
      Hideaki Nakamura
    • Journal Title

      J Controlled Release

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] The EPR effect and beyond for cancer selective drug delivery and imaging.2013

    • Author(s)
      Maeda H, Nakamura H, Tsukigawa K, Fang J.
    • Organizer
      ICBS2013 in Tsukuba.
    • Place of Presentation
      Tsukuba, Japan
    • Related Report
      2012 Final Research Report
  • [Presentation] The EPR effect and beyond for cancer selective drug delivery and imaging2013

    • Author(s)
      Hiroshi Maeda
    • Organizer
      ICBS2013 in Tsukuba
    • Place of Presentation
      つくば
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Tumor targeted imaging and photodynamic therapy by HPMA-polymer conjugated Zn-protophyrin micelle.2012

    • Author(s)
      Fang J, Nakamura H, Qin H, Subr V, Hitaka Y, Ulbrich K, Maeda H.
    • Organizer
      71thAnnual Meeting of the Japanese Cancer Association.
    • Place of Presentation
      Sapporo, Japan 1247815KA003 Nakamura H, Liao L, Subr V, Hitaka Y, Tsukigawa K, Fang J, Ulbrich K, Maeda H.
    • Related Report
      2012 Final Research Report
  • [Presentation] Tumor selective delivery of Zn-Protoporphyrin conjugated hydroxypropylmethacrylamide polymer (HPMA) micelle for imaging and light induced antitumor effect.2012

    • Organizer
      The 39th Annual Meeting and Exposition of the Controlled Release Society.
    • Place of Presentation
      Quebec city, Canada
    • Related Report
      2012 Final Research Report
  • [Presentation] The EPR effect as seen by tumor imaging of fluorescent proteins and synthetic nanoparticles.2012

    • Author(s)
      Maeda H, Nakamura H, Qin H, Tsukigawa K, Fang J.
    • Organizer
      9th International Symposium on Polymer Therapeutics.
    • Place of Presentation
      Valencia, Spain
    • Related Report
      2012 Final Research Report
  • [Presentation] The EPR effect as seen by tumor imaging of fluorescent proteins and synthetic nanoparticles2012

    • Author(s)
      Hiroshi Maeda
    • Organizer
      9th International Symposium on Polymer Therapeutics
    • Place of Presentation
      Valencia, Spain
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Tumor targeting polymeric drugs based on the EPR effect; its augmentation for drug delivery and efficacy, and extension to tumor imaging2012

    • Author(s)
      Hiroshi Maeda
    • Organizer
      77th Microsymposium of Prague Meetings on Macromolecules, Polymers in Medicine
    • Place of Presentation
      Prague, Czech Republic
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Tumor selective delivery of Zn-Protoporphyrin conjugated hydroxypropylmethacrylamide polymer (HPMA) micelle for imaging and light induced antitumor effect2012

    • Author(s)
      Hideaki Nakamura
    • Organizer
      The 39th Annual Meeting and Exposition of the Controlled Release Society
    • Place of Presentation
      Quebec city, Canada
    • Related Report
      2012 Annual Research Report
  • [Presentation] Tumor targeted imaging and photodynamic therapy by HPMA-polymer conjugated Zn-protophyrin micelle.2012

    • Author(s)
      Jun Fang
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] Distinct tumor targeting and fluorescent imaging using nanoparticle based on EPR effect: Toward fluorescent endoscopy2012

    • Author(s)
      Hiroshi Maeda
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Annual Research Report
  • [Presentation] Stability and PEG cleavage of PEGylated zinc protophyrin (PEG-ZnPP) micelle for efficient antitumor effect2011

    • Author(s)
      Kenji Tsukigawa, et al
    • Organizer
      Workshop of Young Cancer Researcher 2011
    • Place of Presentation
      長野
    • Year and Date
      2011-09-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] The importance of cleavage of PEG chains from pegylated zinc protoporphyrin (PEG-ZnPP) by tumor proteases on intracellular uptake2011

    • Author(s)
      Kenji Tsukigawa, Hideaki Nakamura, Jun Fang, et al
    • Organizer
      The 38th Annual Meeting and Exposition of the Controlled Release Society
    • Place of Presentation
      National Harbor, MD, U.S.A
    • Year and Date
      2011-08-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] Stability of PEG-zinc protoporphyrin (PEG-ZnPP) and the improved intracellular uptake by cleavage of PEG chains in tumor site2011

    • Author(s)
      Kenji Tsukigawa, Hideaki Nakamura, Jun Fang, et al
    • Organizer
      第27回日本DDS学会
    • Place of Presentation
      東京
    • Year and Date
      2011-06-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] The importance of cleavage of PEG chains from pegylated zinc protoporphyrin (PEG-ZnPP) by tumor proteases on intracellular uptake.2011

    • Author(s)
      Tsukigawa K, Nakamura H, Fang J, Shinkai S, Maeda H.
    • Organizer
      The 38th Annual Meeting and Exposition of the Controlled Release Society.
    • Place of Presentation
      National Harbor, Maryland, USA
    • Related Report
      2012 Final Research Report
  • [Presentation] 水溶性亜鉛プロトポルフィリンミセルによる抗腫瘍効果とLED光源420nmによる光増感作用2010

    • Author(s)
      覃海波
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pegylated hemin, a water-soluble micelle with therapeutic potential against ischemia-reperfusion injury via induction of heme oxygenase-12010

    • Author(s)
      方軍
    • Organizer
      Annual Meeting of Controlled Release Society 2010
    • Place of Presentation
      Oregon Convention Center, Portland, Oregon, USA
    • Year and Date
      2010-07-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] Intracellular uptake of water-soluble ZnPP micelles (SMA-ZnPP and PEG-ZnPP) and the unique release mechanism of the drug from their micelles.2010

    • Author(s)
      Nakamura H, Qin H, Bharate GY, Tsukigawa K, Fang J, Maeda H.
    • Organizer
      The 37th Annual Meeting and Exposition of the Controlled Release Society.
    • Place of Presentation
      Portland, USA
    • Related Report
      2012 Final Research Report
  • [Book] PEGylated zinc protoporphyrin: a micelle forming polymeric drug for cancer therapy.2012

    • Author(s)
      Fang J, Nakamura H, Seki T, Qin H, Bharate GY, Maeda H.
    • Publisher
      Nanotechnology in Health Care, Singapore, Pan Stanford Publisher
    • Related Report
      2012 Final Research Report
  • [Book] Nanotechnology in Health Care2012

    • Author(s)
      Jun Fang
    • Total Pages
      400
    • Publisher
      Pan Stanford Publisher
    • Related Report
      2012 Annual Research Report
  • [Book] PEGylated Zinc Protoporphyrin : A Micelle Forming Polymeric Drug for Cancer Therapy in Nanotechnology in Health Care (Ed.Sanjeeb Sahoo)2011

    • Author(s)
      Jun Fang
    • Publisher
      Pan Stanford Publishing Pte Ltd.(In press)
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 高分子型蛍光分子プローブ2012

    • Inventor(s)
      前田浩
    • Industrial Property Rights Holder
      前田浩
    • Filing Date
      2012-09-05
    • Related Report
      2012 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 高分子型蛍光分子プローブ2012

    • Inventor(s)
      前田 浩
    • Industrial Property Rights Holder
      前田 浩
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-09-05
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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