Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Key Laboratory of Advanced Technologies of Materials, Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Biomaterials. 2014 Oct;35(30):8711-22. doi: 10.1016/j.biomaterials.2014.06.036. Epub 2014 Jul 4.
In cancer therapy nanocargos based on star-shaped polymer exhibit unique features such as better stability, smaller size distribution and higher drug capacity in comparison to linear polymeric micelles. In this study, we developed a multifunctional star-shaped micellar system by combination of active targeting ability and redox-responsive behavior. The star-shaped micelles with good stability were self-assembled from four-arm poly(ε-caprolactone)-poly(ethylene glycol) copolymer. The redox-responsive behaviors of these micelles triggered by glutathione were evaluated from the changes of micellar size, morphology and molecular weight. In vitro drug release profiles exhibited that in a stimulated normal physiological environment, the redox-responsive star-shaped micelles could maintain good stability, whereas in a reducing and acid environment similar with that of tumor cells, the encapsulated agent was promptly released. In vitro cellular uptake and subcellular localization of these micelles were further studied with confocal laser scanning microscopy and flow cytometry against the human cervical cancer cell line HeLa. In vivo and ex vivo DOX fluorescence imaging displayed that these FA-functionalized star-shaped micelles possessed much better specificity to target solid tumor. Both the qualitative and quantitative results of the antitumor effect in 4T1 tumor-bearing BALB/c mice demonstrated that these redox-responsive star-shaped micelles have a high therapeutic efficiency to artificial solid tumor. Therefore, the multifunctional star-shaped micelles are a potential platform for targeted anticancer drug delivery.
在癌症治疗中，与线性聚合物胶束相比，基于星形聚合物的纳米载药具有更好的稳定性、更小的粒径分布和更高的载药量等独特性质。在这项研究中，我们通过结合主动靶向能力和氧化还原响应行为，开发了一种多功能星形胶束体系。由四臂聚（ε-己内酯）-聚乙二醇共聚物自组装形成具有良好稳定性的氧化还原响应星形胶束。通过胶束粒径、形态和分子量的变化来评估谷胱甘肽触发的这些胶束的氧化还原响应行为。体外药物释放曲线表明，在刺激的正常生理环境中，氧化还原响应星形胶束能够保持良好的稳定性，而在类似于肿瘤细胞的还原和酸性环境中，包封的药物则迅速释放。进一步通过共聚焦激光扫描显微镜和流式细胞术研究了这些胶束对人宫颈癌 HeLa 细胞系的细胞摄取和亚细胞定位。体内和离体 DOX 荧光成像显示，这些 FA 功能化星形胶束对实体肿瘤具有更好的靶向特异性。在 4T1 荷瘤 BALB/c 小鼠中的抗肿瘤效果的定性和定量结果均表明，这些氧化还原响应星形胶束对人工实体瘤具有很高的治疗效率。因此，多功能星形胶束是一种有前途的靶向抗癌药物递送平台。
