Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin.
Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin.
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通过纳米载体介导的 siRNA 和阿霉素共传递增强卵巢癌细胞的凋亡
DOI：
10.2147/ijn.s29328
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发表时间：
2012
影响因子：
8
通讯作者：
Shuai X
中科院分区：
文献类型：
--
作者：
Zou S;Cao N;Cheng D;Zheng R;Wang J;Zhu K;Shuai X
合成了聚乙二醇（PEG）、聚（乙烯亚胺）（PEI）和聚（ε-己内酯）（PCL）的叶酸共轭三元共聚物FA-PEG-PEI-PCL。该共聚物自组装成阳离子胶束，能够共同递送 siRNA 和抗癌药物阿霉素 (DOX)。这种双功能纳米载体在药物/siRNA 递送中表现出低细胞毒性和高性能。使用叶酸靶向纳米载体同时递送针对 Bcl-2 基因的 siRNA 和 DOX 后，通过下调抗凋亡蛋白 Bcl-2，同时上调促凋亡蛋白 Bax 的机制，DOX 诱导过表达叶酸受体的 skov-3 细胞凋亡显着增强。这项工作表明，基于我们的双功能纳米载体，Bcl-2 siRNA 和 DOX 疗法的组合是可行的，这为未来的体内测试奠定了良好的基础。
A folate conjugated ternary copolymer, FA–PEG–PEI–PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ɛ-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.