State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.
Phys Chem Chem Phys. 2013 Sep 14;15(34):14210-8. doi: 10.1039/c3cp51947c. Epub 2013 Jul 24.
Mesoporous silica nanoparticles (MSN)-polymer hybrid combined with the aliphatic biodegradable polyester caps on the surface were first developed in order to manipulate the smart intracellular release of anticancer drugs. First, poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-PCL) was successfully grafted on the surface of MSN via disulfide bonds which could cleave under a reduction environment in tumor cells. The anticancer drug doxorubicin (DOX) was encapsulated into the particle pores. The in vitro drug release profile showed that DOX release was significantly restricted by the polymer caps at pH 7.4, while it was greatly accelerated upon the addition of GSH. Cytotoxicity evaluation showed good biocompatibility with the hybrid particles. Fast endocytosis and intracellular DOX release were observed by confocal laser scanning microscopy (CLSM). The DOX-loaded particles exhibited comparable antitumor activity with free DOX towards HeLa cells and showed in a time-dependent manner. This work developed an extensive method of utilizing aliphatic biodegradable polyesters as polymer caps for MSN to control drug delivery. The paper might offer a potential option for cancer therapy.
为了控制抗癌药物的智能细胞内释放，首次开发了介孔硅纳米粒子（MSN）-聚合物杂化体，并在表面结合了脂肪族可生物降解聚酯帽。首先，通过二硫键成功地将聚（乙二醇）-b-聚（ε-己内酯）（PEG-PCL）接枝到 MSN 表面，该二硫键可以在肿瘤细胞的还原环境中裂解。将抗癌药物阿霉素（DOX）封装到颗粒孔中。体外药物释放曲线表明，在 pH 7.4 时，聚合物帽显著限制了 DOX 的释放，而在添加 GSH 后，释放速度大大加快。细胞毒性评估显示杂化颗粒具有良好的生物相容性。通过共聚焦激光扫描显微镜（CLSM）观察到快速的内吞作用和细胞内 DOX 释放。负载 DOX 的颗粒对 HeLa 细胞表现出与游离 DOX 相当的抗肿瘤活性，并呈现出时间依赖性。这项工作开发了一种广泛的方法，利用脂肪族可生物降解聚酯作为 MSN 的聚合物帽来控制药物传递。该论文可能为癌症治疗提供了一种潜在的选择。
