Xu Zhigang, Liu Shiying, Kang Yuejun, Wang Mingfeng
School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
Nanoscale. 2015 Mar 19;7(13):5859-68. doi: 10.1039/c5nr00297d.
A myriad of drug delivery systems such as liposomes, micelles, polymers and inorganic nanoparticles (NPs) have been developed for cancer therapy. Very few of them, however, have the ability to integrate multiple functionalities such as specific delivery, high circulation stability, controllable release and good biocompatibility and biodegradability in a single system to improve the therapeutic efficacy. Herein, we report two types of stimuli-responsive nonporous silica prodrug NPs towards this goal for controlled release of anticancer drugs and efficient combinatorial cancer therapy. As a proof of concept, anticancer drugs camptothecin (CPT) and doxorubicin (DOX) were covalently encapsulated into silica matrices through glutathione (GSH)-responsive disulfide and pH-responsive hydrazone bonds, respectively, resulting in NPs with sizes tunable in the range of 50-200 nm. Both silica prodrug NPs showed stimuli-responsive controlled release upon exposure to a GSH-rich or acidic environment, resulting in improved anticancer efficacy. Notably, two prodrug NPs simultaneously taken up by HeLa cells showed a remarkable combinatorial efficacy compared to free drug pairs. These results suggest that the stimuli-responsive silica prodrug NPs are promising anticancer drug carriers for efficient cancer therapy.
为了癌症治疗，人们已经开发出了无数种药物递送系统，如脂质体、胶束、聚合物和无机纳米颗粒（NPs）。然而，其中很少有能够在单一系统中整合多种功能的，比如特异性递送、高循环稳定性、可控释放以及良好的生物相容性和生物降解性，以提高治疗效果。在此，我们报道了两种刺激响应型无孔二氧化硅前药纳米颗粒，旨在实现抗癌药物的可控释放和高效联合癌症治疗。作为概念验证，抗癌药物喜树碱（CPT）和阿霉素（DOX）分别通过谷胱甘肽（GSH）响应性二硫键和pH响应性腙键共价封装到二氧化硅基质中，得到尺寸在50 - 200 nm范围内可调的纳米颗粒。两种二氧化硅前药纳米颗粒在暴露于富含GSH或酸性环境时均表现出刺激响应性可控释放，从而提高了抗癌效果。值得注意的是，与游离药物组合相比，被HeLa细胞同时摄取的两种前药纳米颗粒显示出显著的联合疗效。这些结果表明，刺激响应型二氧化硅前药纳米颗粒是用于高效癌症治疗的有前景的抗癌药物载体。
