New oligonucleotide therapeutics using polymeric nano-micelles conjugated with tumor suppressive microRNA in bladder cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09198
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kagoshima University
• Principal Investigator: YAMADA Yasutoshi 鹿児島大学, 医歯学域医学系, 講師 (40437968)
• Co-Investigator(Kenkyū-buntansha): 榎田 英樹 鹿児島大学, 医歯学域医学系, 准教授 (80347103) ; 吉野 裕史 鹿児島大学, 医歯学域医学系, 助教 (90642611)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 膀胱癌 / microRNA / ナノミセル / ドラッグデリバリー / miR-218 / miR-1

Outline of Final Research Achievements

We synthesized chimeric double strand microRNA (miR) containing nucleotide sequence of tumor suppressive miR-218. When miR-218 conjugated with unit PIC administrated to bladder cancer (BC) cell lines, the intra-cellular concentration of miR-218 increased more than one hundred time compared to before administration. Apoptosis was induced in the treated cells by the MagicRed analysis. Next, administrating the exosome with high expression of tumor suppressive miR-1 to BC cells repressed cell proliferation, migration and invasion compared to the controls. In vivo study showed that the xenograft size was significantly reduced in the mice with injection of the miR-1 exosome compared to the controls.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

一連の研究により、癌抑制型マイクロRNAをin vitroあるいはin vivoで投与する新規マイクロＲＮＡ投与手段を開発できた。さらに抗腫瘍効果を確認できた。最適化のためさらなる条件の検討が必要ではあるが、これまでin vitroでリポフェクタミン法によるトランスフェクションしか導入手段がなかったため、今後、癌抑制型マイクロRNAの臨床応用の可能性を拓くことが出来たことは学術的意義が大きい。実臨床で治療手段の少ない膀胱癌患者にとって福音となり得る。