Development of smart MRI contrast agents based on polymeric micelles to detect tumor microenvironment

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670010
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: NISHIYAMA Nobuhiro 東京工業大学, 資源化学研究所, 教授 (10372385)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 高分子ミセル / がん / イメージング / MRI / 低酸素領域 / 微小転移 / 診断

Outline of Final Research Achievements

To improve the accuracy of MR imaging, the development of tumor-specific MRI contrast agents have been strongly demanded. In this study, we have developed polymeric micelles composed of calcium phosphate core, which can exhibit dissolution responding to acidic pH environment in the tumor tissue and incorporated Mn2+ ions, an MRI contrast agent, into the micelles. Polymeric micelles could release Mn2+ ions selectively under the acidic conditions mimicking the tumor microenvironments, and the released Mn2+ ions showed T1 shortening through the interaction with proteins. The in vivo experiments revealed that Mn2+ ions-loaded micelles displayed remarkably enhanced tumor-specific contrast enhancement compared with clinically used MRI contrast agents. Also, the Mn2+ ions-loaded micelles have been demonstrated to be useful for MR imaging of tumor hypoxia and small metastases in the liver.

Free Research Field

バイオマテリアル、ドラッグデリバリーシステム