Ligand-Linked Polymeric Micelles for Targeted Delivery of Platinum Anti-Cancer Drug into Malignant Tumor

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659584
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: The University of Tokyo
• Principal Investigator: MIURA Yutaka 東京大学, 医学(系)研究科(研究院), 助教 (40557980)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ドラッグデリバリー / ナノ材料 / 脳腫瘍

Outline of Final Research Achievements

The installation of ligand molecules such as peptides onto nanocarriers is now considered an important strategy to improve the selectivity of drug delivery. Among these ligands, Arg-Gly-Asp (RGD) peptides are promising ligand molecules for targeting alpha v beta 3 integrins, which are overexpressed in angiogenic sites and tumors, such as human glioblastoma (U87MG). In this study, the cyclic RGD was introduced to the maleimide-surface functionalized dichloro(1,2-diamino-cyclohexane)platinum(II)-loaded micelles by Michael addition reaction. Intravital confocal laser scanning microscopy revealed that the cRGD-linked polymeric micelles (cRGD/m) accumulated rapidly and had high permeability from vessels into the tumor parenchyma. It was confirmed that the selective and accelerated accumulation of cRGD/m into tumors occurred via an active internalization pathway, possibly transcytosis, thereby producing significant anti-tumor effects in an orthotopic mouse model of U87MG human glioblastoma.

Free Research Field

臨床医工学