Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA.
Inhibition of cell proliferation through an ATP-responsive co-delivery system of doxorubicin and Bcl-2 siRNA.
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通过阿霉素和 Bcl-2 siRNA 的 ATP 响应共传递系统抑制细胞增殖
DOI：
10.2147/ijn.s135086
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发表时间：
2017
影响因子：
8
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhang J;Wang Y;Chen J;Liang X;Han H;Yang Y;Li Q;Wang Y
本文通过三磷酸腺苷（ATP）响应适体与其cDNA杂交构建DNA双链体，其中富含GC的基序可用于负载阿霉素（DOX），然后以阳离子聚合物PEI25K为载体，同时缩合DOX-Duplex和Bcl-2 siRNA，制备三元纳米复合物聚乙烯亚胺（PEI）/DOX-Duplex/siRNA。细胞质和细胞外环境之间的ATP浓度梯度可以实现双链体中DOX的稳定负载和ATP响应方式的快速药物释放。以人前列腺肿瘤细胞系PC-3为模型，可以检测到明显的细胞增殖诱导，细胞活力为53.3%，比单一货物递送更强，表明这两种成分之间的协同作用。三元纳米复合物增强的抗增殖作用可能归因于线粒体介导途径中细胞凋亡的诱导改善以及细胞周期停滞在 G2 期。总体而言，用于共同递送DOX和Bcl-2 siRNA的ATP响应纳米载体已被证明是一种具有良好抗增殖作用的智能递送系统，特别是对于解决肿瘤的多药耐药性。
Herein, DNA duplex was constructed through the hybridization of adenosine triphosphate (ATP)-responsive aptamer and its cDNA in which GC-rich motif could be used to load doxorubicin (DOX), and then, cationic polymer PEI25K was used as a carrier to simultaneously condense DOX-Duplex and Bcl-2 siRNA to prepare the ternary nanocomplex polyethylenimine (PEI)/DOX-Duplex/siRNA. The ATP concentration gradient between the cytosol and extracellular environment could achieve the stable loading of DOX in duplex and the rapid drug release in an ATP-responsive manner. Using human prostate tumor cell line PC-3 as a model, an obvious induction of cell proliferation could be detected with a cell viability of 53.3%, which was stronger than single cargo delivery, indicating the synergistic effect between these two components. The enhanced anti-proliferative effect of ternary nanocomplex could be attributed to the improved induction of cell apoptosis in a mitochondria-mediated pathway and cell-cycle arrest at the G2 phase. Overall, the ATP-responsive nanocarrier for co-delivering DOX and Bcl-2 siRNA has been demonstrated to be a smart delivery system with favorable anti-proliferative effect, especially for solving the multidrug resistance of tumors.