Effect of the size of ligand-conjugated nanocarriers on their accumulation and therapeutic effect in solid tumors

2014 Fiscal Year Final Research Report

• Project/Area Number: 25750172
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: The University of Tokyo
• Principal Investigator: CABRAL Horacio 東京大学, 工学(系)研究科(研究院), 准教授 (10533911)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: ドラッグデリバリー / 環状RGDペプチド / ナノ粒子のサイズ / アクティブターゲティング / 高分子ミセル / グリオーマ

Outline of Final Research Achievements

The aim was to evaluate the size effect of ligand-installed nanomedicines in their ability to target solid tumors. Drug-loaded micelles having 30-, 50-, 70- and 100-nm diameter were prepared, and conjugated with cyclic-RGD (cRGD) peptide for targeting of tumors overexpressing avb3 and avb5 integrins. cRGD-installed micelles (cRGD/m) showed comparable stability and drug release rates. The in vitro activity of cRGD/m against monolayer culture of glioma U87-MG cells showed that all cRGD/m had comparable cytotoxicity. In vivo, 30- and 50-nm cRGD/m suppressed the growth of U87-MG xenografts, while larger cRGD/m failed to show antitumor activity. Tumor accumulation was around 8% of injected dose per gram of tissue for 30- and 50-nm cRGD/m, whereas larger cRGD/m were lower than 2%. In vivo CLSM showed cRGD/m with 30-nm penetrated into U87-MG tumors, whereas 70-nm cRGD/m did not extravasate, indicating a size-mediated active transport mechanism.

Free Research Field

ナノメヂジン