| Project/Area Number |
17H06641
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Otorhinolaryngology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Miyano Kazuki 東京大学, 医学部附属病院, 登録研究員 (50801213)
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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.
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| 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。
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