Lin Jian-Tao, Liu Zong-Kun, Zhu Qing-Ling, Rong Xiao-Hui, Liang Cui-Ling, Wang Jie, Ma Dong, Sun Jing, Wang Guan-Hai
Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang 523024, China; Traditional Chinese Medicine and New Drug Research Institute, Guangdong Medical University, Dongguan, 523808, China.
The Third People's Hospital of Jiaozhou, Qiaodao, 266300, China.
Colloids Surf B Biointerfaces. 2017 Jul 1;155:41-50. doi: 10.1016/j.colsurfb.2017.04.002. Epub 2017 Apr 5.
Stimuli-responsive nanocarriers for anticancer drug and gene co-delivery are promising strategy in cancer therapy. The ultimate goal is to deliver high local concentration of therapeutic agents with no premature release and result in synergistic effects for combination therapies. In this work, we developed a redox stimuli-responsive and synergistic co-delivery system for anticancer drug DOX and p53 gene for potential cancer therapy. A dendronized chitosan derivative (CP) as a "gatekeeper" to control release the drug was used to modify MSNs via a disulfide linker and improve the gene transfection efficiency. Stimulus-induced release of the DOX was studied in the presence of glutathione (GSH), which showed that polymer shell was shed and accelerated the release of embedded drugs inside the tumor cells under a GSH-rich environment. The obtained nanoparticles showed good gene delivery ability in vitro by inducing an obvious increase in p53 protein expression in Hela cells. Apoptosis analysis confirmed that DOX and p53 could be co-delivered to the Hela cells by MSN-SS-CP nanocarriers and induced significant cell apoptosis. These results demonstrated that the dual delivery system resulted in synergistic effects and lead to an effective cancer cell apoptosis, which may be promising for cancer therapeutic application.
用于抗癌药物和基因共递送的刺激响应性纳米载体是癌症治疗中有前景的策略。最终目标是在不提前释放的情况下递送高局部浓度的治疗剂，并产生联合治疗的协同效应。在这项工作中，我们开发了一种用于抗癌药物阿霉素（DOX）和p53基因的氧化还原刺激响应性协同共递送系统，用于潜在的癌症治疗。一种作为“守门人”来控制药物释放的树枝状壳聚糖衍生物（CP）通过二硫键连接用于修饰介孔二氧化硅纳米颗粒（MSNs），并提高基因转染效率。在谷胱甘肽（GSH）存在的情况下研究了阿霉素的刺激诱导释放，结果表明在富含GSH的环境中，聚合物壳脱落并加速了肿瘤细胞内包封药物的释放。所获得的纳米颗粒通过诱导Hela细胞中p53蛋白表达明显增加，在体外显示出良好的基因递送能力。凋亡分析证实，阿霉素和p53可以通过MSN-SS-CP纳米载体共递送至Hela细胞，并诱导显著的细胞凋亡。这些结果表明，双递送系统产生了协同效应并导致有效的癌细胞凋亡，这可能在癌症治疗应用中具有前景。
