Yang Yihua, Wang Zhe, Peng Ying, Ding Jinsong, Zhou Wenhu
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China.
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmaceutical Sciences, Xuzhou Medical University, Xuzhou, China.
Front Pharmacol. 2019 Jan 24;10:10. doi: 10.3389/fphar.2019.00010. eCollection 2019.
Micelles are highly attractive nano-drug delivery systems for targeted cancer therapy. While they have been demonstrated to significantly alleviate the side-effects of their cargo drugs, the therapy outcomes are usually suboptimal partially due to ineffective drug release and endosome entrapment. Stimulus-responsive nanoparticles have allowed controlled drug release in a smart fashion, and we want to use this concept to design novel micelles. Herein, we reported pH-sensitive paclitaxel (PTX)-loaded poly (ethylene glycol)-phenylhydrazone-dilaurate (PEG-BHyd-dC) micelles (PEG-BHyd-dC/PTX). The micelles were spherical, with an average particle size of ∼135 nm and a uniform size distribution. The pH-responsive properties of the micelles were certified by both colloidal stability and drug release profile, where the particle size was strikingly increased accompanied by faster drug release as pH decreased from 7.4 to 5.5. As a result, the micelles exhibited much stronger cytotoxicity than the pH-insensitive counterpart micelles against various types of cancer cells due to the hydrolysis of the building block polymers and subsequent rapid PTX release. Overall, these results demonstrate that the PEG-BHyd-dC micelle is a promising drug delivery system for cancer therapy.
胶束是用于靶向癌症治疗的极具吸引力的纳米药物递送系统。虽然已证明它们能显著减轻所载药物的副作用，但治疗效果通常并不理想，部分原因是药物释放无效和被内体截留。刺激响应性纳米颗粒能够以智能方式实现可控药物释放，我们希望利用这一概念设计新型胶束。在此，我们报道了负载pH敏感型紫杉醇（PTX）的聚（乙二醇）-苯腙-二月桂酸酯（PEG-BHyd-dC）胶束（PEG-BHyd-dC/PTX）。这些胶束呈球形，平均粒径约为135 nm，粒径分布均匀。胶束的pH响应特性通过胶体稳定性和药物释放曲线得到证实，当pH从7.4降至5.5时，粒径显著增大，同时药物释放加快。结果，由于构建聚合物的水解以及随后PTX的快速释放，与pH不敏感的对照胶束相比，这些胶束对各种类型的癌细胞表现出更强的细胞毒性。总体而言，这些结果表明PEG-BHyd-dC胶束是一种有前景的癌症治疗药物递送系统。
