Targeting peptide iRGD-conjugated amphiphilic chitosan-co-PLA/DPPE drug delivery system for enhanced tumor therapy

文献类型： 外文期刊

第一作者： Zhang, Jiakun

作者： Zhang, Jiakun;Xu, Qing;Liu, Xiaoguang;Wu, Yan;Chen, Chunying;Zhang, Jiakun;Li, Yaping

作者机构：

期刊名称：JOURNAL OF MATERIALS CHEMISTRY B （ 影响因子：6.331； 五年影响因子：5.726 ）

ISSN： 2050-750X

年卷期： 2014 年 2 卷 21 期

页码：

收录情况： SCI

摘要： In this paper, we report a novel targeting drug delivery system, obtained using an amphiphilic chitosan-co-(D,L-lactide)/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer (CS-co-PLA/DPPE) with the modification of an iRGD (CRGDKGPDC) peptide as the targeting module. Hydrophilic doxorubicin (DOX) was encapsulated and cell experiments were carried out to evaluate the anti-tumor efficacy of DOX-loaded nanoparticles (NPs) in vitro. Characterization data showed a favorable size distribution, high encapsulation efficiency and a pH-dependent release profile for the synthesized NPs. A cytotoxicity assay revealed the higher inhibitory effect of DOX-iRGD-NPs especially in cell lines with an abundant expression of alpha(v)beta(3) integrin receptors. An increased cellular uptake of DOX-iRGD-NPs was observed and further confirmed to be a consequence of a specific endocytosis pathway mediated by ligand-receptor interactions. Visualization of the intracellular trafficking showed different distributions of DOX when delivered using DOX-NPs and DOX-iRGD-NPs, proving the targeting effect of iRGD. With the help of the iRGD targeting peptide, a chemotherapeutic drug can be delivered specifically to the cancer and endothelial cells expressing alpha(v)beta(3) integrin receptors to achieve an enhanced anti-tumor efficacy and controlled drug release.

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