Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiao Tong University, Shanghai, 200240, China.
College of Textile and Clothing, Yancheng Institute of Technology, Yancheng, 224051, China.
Colloids Surf B Biointerfaces. 2019 Aug 1;180:58-67. doi: 10.1016/j.colsurfb.2019.04.042. Epub 2019 Apr 18.
Development of polymer-drug conjugate capable of controlled drug release is urgently needed for gastric cancer therapy. Herein, arginine-glycine-aspartic acid (RGD)-decorated polyethylene glycol (PEG)-paclitaxel (PTX) conjugates containing disulfide linkage were synthesized. The amphiphilic PEG-PTX conjugates were found to assemble into micelles (RGD@Micelles), which would be decomposed under the reduction of glutathione (GSH) and finally release PTX in weakly acidic conditions characteristic of intracellular environment. The RGD@Micelles were spherical nanoparticles with an average hydrodynamic size of ˜50 nm, which were stable in physiological environment. The release of PTX from the micelles in response to GSH was investigated. In vitro cell assay suggested that the RGD@Micelles could target the gastric cancer cells and inhibit cell proliferation by inducing apoptosis. In vivo experiments indicated that the RGD@Micelles could be delivered to the tumor site and inhibit the tumor growth efficiently by releasing PTX inside the tumor cells. This type of micelles exhibited high therapeutic efficacy and low side effects, providing new insights into targeted drug delivery for gastric cancer therapy.
用于胃癌治疗的聚合物-药物偶联物的可控药物释放的开发迫在眉睫。在此，合成了精氨酸-甘氨酸-天冬氨酸（RGD）修饰的聚乙二醇（PEG）-紫杉醇（PTX）缀合物，其中含有二硫键。两亲性 PEG-PTX 缀合物被发现自组装成胶束（RGD@Micelles），在谷胱甘肽（GSH）的还原下会分解，最终在细胞内环境特有的弱酸性条件下释放 PTX。RGD@Micelles 是平均水动力直径约为 50nm 的球形纳米颗粒，在生理环境中稳定。研究了 GSH 响应下胶束中 PTX 的释放情况。体外细胞实验表明，RGD@Micelles 可以通过诱导细胞凋亡靶向胃癌细胞并抑制细胞增殖。体内实验表明，RGD@Micelles 可以通过在肿瘤细胞内释放 PTX 递送到肿瘤部位并有效抑制肿瘤生长。这种胶束表现出高治疗效果和低副作用，为胃癌治疗的靶向药物输送提供了新的思路。
