a Department of Oncology , the Jilin Central Hospital of Jilin University , Jilin , China.
J Biomater Sci Polym Ed. 2019 Feb;30(3):233-246. doi: 10.1080/09205063.2019.1565612. Epub 2019 Jan 16.
Micelles are promising a nano drug carrier for cancer therapy. However, their application is often limited due to the instability of them in vivo. Herein, we reported the development of stereocomplex micelle (SCM) based on amphiphilic dextran-block-polylactide (Dex-b-PLA) that could improve the stability of micelles, reduce the early release of loaded drugs and target the breast cancer through the enhanced permeability and retention (EPR) effect for enhanced breast cancer therapy. The SCM were fabricated from the equimolar mixture of the enantiomeric Dex-b-PLA copolymers. Paclitaxel (PTX) as a model anti breast cancer drug was loaded in the SCM, noted as SCM/PTX. Transmission electron microscopy (TEM) and dynamic laser scattering (DLS) showed the diameter of SCM/PTX was below100 nm, which was suitable sizes for the EPR effect. The release kinetics of SCM/PTX exhibited that the release of PTX was obviously slow down and showed constant release. In the in vitro antitumor test, the SCM/PTX could effectively suppress the viability of 4T1 cells, which was demonstrated by the MTT assay. Moreover, the SCM/PTX could reduce the distribution of PTX at normal organs and obviously increase the accumulation of PTX at tumor sites. The circulation time of SCM/PTX was also obviously enhanced compared to free PTX. In the in vivo antitumor test, the SCM/PTX effectively inhibited the progression of 4T1 breast cancer in the orthotopic mouse model, as demonstrated by decreased tumor growth and increased apoptosis and necrosis areas within tumor tissues. In addition, the toxic side effects of PTX was also alleviated in the SCM/PTX group. This study introduced a stable micelle system that passive targeted the tumor for enhanced breast cancer therapy.
胶束是一种很有前途的纳米药物载体，可用于癌症治疗。然而，由于其在体内的不稳定性，它们的应用往往受到限制。在此，我们报道了基于两亲性葡聚糖嵌段-聚乳酸（Dex-b-PLA）的立体复合物胶束（SCM）的发展，该胶束可以提高胶束的稳定性，减少载药的早期释放，并通过增强通透性和保留（EPR）效应来靶向乳腺癌，从而增强乳腺癌的治疗效果。SCM 是由等摩尔比的对映体 Dex-b-PLA 嵌段共聚物组成。紫杉醇（PTX）作为一种模型抗乳腺癌药物被负载在 SCM 中，记为 SCM/PTX。透射电子显微镜（TEM）和动态激光散射（DLS）显示 SCM/PTX 的直径小于 100nm，适合 EPR 效应。SCM/PTX 的释放动力学表明，PTX 的释放明显减慢并呈现恒速释放。在体外抗肿瘤试验中，SCM/PTX 能够有效抑制 4T1 细胞的活力，这可以通过 MTT 试验来证明。此外，SCM/PTX 可以减少 PTX 在正常器官中的分布，并明显增加肿瘤部位 PTX 的积累。与游离 PTX 相比，SCM/PTX 的循环时间也明显延长。在体内抗肿瘤试验中，SCM/PTX 有效抑制了原位小鼠模型中 4T1 乳腺癌的进展，表现为肿瘤生长的减少以及肿瘤组织中凋亡和坏死区域的增加。此外，SCM/PTX 还减轻了 PTX 的毒副作用。本研究介绍了一种被动靶向肿瘤的稳定胶束系统，可用于增强乳腺癌的治疗。
