中文  English

Tel: +86-431-85262367
Fax: +86-431-85262933
E-mail: xiaocs@ciac.ac.cn
Add: ChangChun. China 吉ICP备06005930号-1

News

A cooperative polymeric platform for tumor-targeted drug delivery

Author:XCS Date:2015-12-16 15:12:35
 In the pursuit for effective treatments for cancer, the emerging strategy is the "active targeting", where nanoparticles are decorated with targeting ligands able to recognize and bind specific receptors overexpressed by tumor cells or tumor vasculature so that a greater fraction of the administered drugs are selectively trafficked to tumor sites. However, the implementation of this strategy has faced a major obstacle. The interpatient, inter- and intra-tumoral heterogeneity in receptor expression can pose challenges for the design of clinical trials and result in the paucity of targetable receptors within a tumor, which limits the effectiveness of “active targeting” strategy in cancer treatment. Here we report a cooperative drug delivery platform that overcomes the heterogeneity barrier unique to solid tumors. The cooperative platform comprises a coagulation-inducing agent and coagulation-targeted polymeric nanoparticles. As a typical small-molecule vascular disrupting agent (VDA), DMXAA can create a unique artificial coagulation environment with additional binding sites in a solid tumor by locally activating a coagulation cascade. Coagulation-targeted cisplatin-loaded nanoparticles, which are surface-decorated with a substrate of activated blood coagulation factor XIII, can selectively accumulate in the solid tumor by homing to the VDA-induced artificial coagulation environment through transglutamination. In vivo studies show that the cooperative tumor-selective platform recruits up to 7.5-fold increases in therapeutic cargos to the tumors and decreases tumor burden with low systemic toxicity as compared with non-cooperative controls. These indicate that the use of coagulation-targeted nanoparticles, in conjunction with free small-molecule VDAs, may be a valuable strategy for improving standard chemotherapy.

Journal: Chemical Science

Author: Wantong Song, Zhaohui Tang*, Dawei Zhang, Mingqiang Li, Jingkai Gu, Xuesi Chen*

Doi: 10.1039/c5sc01698c.