Development of new treatment with MRI-detectable polymeric micelles incorporating platinum anticancer drugs against hepatocellular carcinoma

Research Project

Project/Area Number	26861067
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Digestive surgery
Research Institution	Shiga University of Medical Science
Principal Investigator	Kaida Sachiko 滋賀医科大学, 医学部, 特任助教 (70710234)
Project Period (FY)	2014-04-01 – 2016-03-31
Project Status	Completed (Fiscal Year 2015)
Budget Amount *help	¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords	高分子ミセル / ドラッグデリバリーシステム / 抗癌剤 / MRI造影剤 / 肝細胞癌 / 肝癌 / ドラッグデリバリー / polymeric micelle / drug delivery / hepatocellular carcinoma / Gd-DTPA / DACHPt
Outline of Final Research Achievements	We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls.