Novel strategy of tumor treatiment via the normalization of tumor vasculature by microRNA

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670018
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: Oku Naoto 静岡県立大学, 薬学部, 教授 (10167322)
• Co-Investigator(Kenkyū-buntansha): ASAI Tomohiro 静岡県立大学, 薬学部, 准教授 (00381731) ; SHIMIZU Kosuke 静岡県立大学, 薬学部, 講師 (30423841)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 核酸医薬品 / RNA干渉 / ポリカチオンリポソーム / がん治療 / マイクロRNA / 血管正常化 / TEPA-PCL / miR499

Outline of Final Research Achievements

Previously, we clarified that miR-499 suppressed tumor growth through the inhibition of vascular endothelial growth factor (VEGF) production and subsequent angiogenesis. In this study, we focused on the genetic therapy using microRNA-499 (miR-499)in combination with chemotherapy for the advanced treatment of cancer.Firstly, tetraethylenepentamine-based polycation liposomes (TEPA-PCL) were prepared and modified with angiogenic vessel-targeted peptide for the delivery of miR-499 (APRPG-miR-499) to angiogenic vessels and tumor cells. The tumor blood flow was significantly improved, after systemic administration of APRPG-miR-499 to colon carcinoma-bearing mice. In addition, the accumulation of doxorubicin (DOX) in the tumors was increased by pre-treatment with APRPG-miR-499. Finally, the combination therapy of APRPG-miR-499 and DOX resulted in significant suppression of the tumor growth.

Free Research Field

薬物送達学