Co-Delivery of Doxorubicin and Anti-BCL-2 siRNA by pH-Responsive Polymeric Vector to Overcome Drug Resistance in In Vitro and In Vivo HepG2 Hepatoma Model
Co-Delivery of Doxorubicin and Anti-BCL-2 siRNA by pH-Responsive Polymeric Vector to Overcome Drug Resistance in In Vitro and In Vivo HepG2 Hepatoma Model
复制标题
通过 pH 响应聚合载体共同递送阿霉素和抗 BCL-2 siRNA 以克服体外和体内 HepG2 肝癌模型的耐药性
DOI：
10.1021/acs.biomac.8b00272
复制
发表时间：
2018-06-01
影响因子：
6.2
通讯作者：
Shuai, Xintao
中科院分区：
文献类型：
--
作者：
Sun, Weitong;Chen, Xiaoyan;Shuai, Xintao
耐药是肿瘤化疗成功的主要障碍，耐药机制多种多样。化疗药物与siRNA联合治疗是一种通过协同作用提高抗癌效果的新策略。本研究首次合成了聚乙二醇-嵌段聚l -赖氨酸-嵌段聚天冬氨酸（N-（N′，N′-二异丙基氨基乙基））（PEG-PLL-PAsp(DIP)）三嵌段共聚物，实现了BCL-2 siRNA与DOX的共递送。该系统不仅可以绕过药物外排，还可以下调抗凋亡基因，从而对抗化学耐药。此外，共递送系统的pH响应能力可以防止药物在循环过程中泄漏，保证药物在肿瘤处的快速释放。共传递siRNA可抑制抗凋亡BCL-2的表达，从而使癌细胞对抗癌药物敏感，提高治疗效果。因此，BCL-2 siRNA与抗癌药物DOX的共递送是一种很有前景的化疗耐药策略。
Drug resistance, developed through multiple mechanisms, is a major hindrance to successful chemotherapy of tumor. Combination therapy of chemo-therapeutic drugs and siRNA represents an emerging strategy which may improve anticancer effect by synergistic actions. In this study, triblock copolymer of poly(ethylene glycol)-block-poly(L-lysine)-block-poly aspartyl (N-(N',N'-diisopropylaminoethyl)) (PEG-PLL-PAsp(DIP)) was synthesized for the first time to enable the codelivery of BCL-2 siRNA and DOX. The system is supposed to not only bypass drug efflux but also down-regulate the antiapoptotic gene and consequently confronting against chemoresistance as well. Moreover, the pH responsive ability of the codelivery system can prevent drug leakage during circulation and guarantee swift drug release at tumors. The codelivered siRNA serves to suppress the expression of antiapoptotic BCL-2 and hence sensitize the cancer cells to anticancer drugs and produce improved therapeutic effect. Consequently, the codelivery of BCL-2 siRNA and anticancer drug DOX serves as a promising strategy against drug resistance in chemotherapy.