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Development of installing cRGD peptide on micellar nanomedicines incorporating cisplatin against cancer stem-like cells

Research Project

Project/Area Number 17H06641
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Otorhinolaryngology
Research InstitutionThe University of Tokyo

Principal Investigator

Miyano Kazuki  東京大学, 医学部附属病院, 登録研究員 (50801213)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsドラッグデリバリーシステム / 高分子ミセル / シスプラチン / リンパ節転移 / がん幹細胞 / ナノバイオ / ドラックデリバリーシステム
Outline of Final Research Achievements

We found that the CSCs (cancer stem-like cells) subpopulation in two HNSCC (head and neck squamous cell carcinoma) cells (human oral carcinoma cells SAS-L1 and HSC-2) overexpresses αvβ5 integrins, which is preferentially expressed in tumor neovasculature and cancer cells and we have modified the CDDP-loaded micelles (CDDP/m) with cyclic Arg-Gly-Asp (cRGD) peptide, which can target αvβ5 integrins, for enhancing their antitumor efficacy against HNSCC. Thus, in this study, we propose installing cRGD peptide on micellar nanomedicines incorporating cisplatin for improving their activity against CSCs and enhancing survival.
cRGD-CDDP/m showed significant antitumor activity against both orthotopic SAS-L1 and HSC-2 tumors in vivo. Moreover, cRGD-CDDP/m rapidly accumulated into the lymph node metastasis of SAS-L1 tumors, effectively inhibiting their growth, and prolonging mice survival.

Academic Significance and Societal Importance of the Research Achievements

今後cRGD-CDDP/mが臨床応用される場合には、転移リンパ節における抗腫瘍効果のみならず、微小転移の可能性があるリンパ節における転移成立阻止効果により、頭頸部扁平上皮癌の治療戦略において既存の予防的頸部郭清術に取って代わる革新的なドラッグデリバリーシステム(DDS)製剤となる事が期待される。また、有害事象が少なくかつ腫瘍選択的な薬剤投与が可能となる事で、社会生活を継続しながらも高い治療効果を享受する事が可能となり、患者本人の経済的負担、並びに副作用対策医療費の軽減が期待され、患者のQOL、医療経済の側面においても多大なメリットがもたらされると考えている。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (4 results)

All 2018 2017

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

  • [Journal Article] cRGD peptide installation on cisplatin-loaded nanomedicines enhances efficacy against locally advanced head and neck squamous cell carcinoma bearing cancer stem-like cells2017

    • Author(s)
      Miyano Kazuki、Cabral Horacio、Miura Yutaka、Matsumoto Yu、Mochida Yuki、Kinoh Hiroaki、Iwata Caname、Nagano Osamu、Saya Hideyuki、Nishiyama Nobuhiro、Kataoka Kazunori、Yamasoba Tatsuya
    • Journal Title

      J Control Release

      Volume: 261 Pages: 275-286

    • DOI

      10.1016/j.jconrel.2017.06.021

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 頭頸部癌に対するリガンド搭載シスプラチンミセルの治療戦略2018

    • Author(s)
      宮野一樹
    • Organizer
      第24回東大・慶大ジョイントカンファレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] 頭頸部癌治療における新たなドラッグデリバリーシステム(DDS)製剤の開発2018

    • Author(s)
      宮野一樹
    • Organizer
      渋谷区耳鼻咽喉科医会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] An active targeting strategy against locally advanced head and neck squamous cell carcinoma harboring cancer stem-like cells via cRGD2017

    • Author(s)
      Miyano K, Cabral H, Miura Y, Matsumoto Y, Mochida Y, Kinoh H, Nishiyama N, Kataoka K, Yamasoba T.
    • Organizer
      14th US-Japan Symposium on Drug Delivery Systems
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-08-25   Modified: 2020-03-30  

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