Reversal of multidrug resistance in MCF-7/Adr cells by codelivery of doxorubicin and BCL2 siRNA using a folic acid-conjugated polyethylenimine hydroxypropyl-β-cyclodextrin nanocarrier.
Reversal of multidrug resistance in MCF-7/Adr cells by codelivery of doxorubicin and BCL2 siRNA using a folic acid-conjugated polyethylenimine hydroxypropyl-β-cyclodextrin nanocarrier.
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使用叶酸缀合的聚乙烯亚胺羟丙基-β-环糊精纳米载体同时递送阿霉素和 BCL2 siRNA，逆转 MCF-7/Adr 细胞的多药耐药性
DOI：
10.2147/ijn.s67146
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发表时间：
2015
影响因子：
8
通讯作者：
Mao ZW
中科院分区：
文献类型：
--
作者：
Li JM;Zhang W;Su H;Wang YY;Tan CP;Ji LN;Mao ZW
全身化疗常面临耐药性，限制了其在肿瘤治疗中的应用。在这项研究中，我们开发了一种简单的多功能纳米载体的聚乙烯亚胺（PEI）的基础上，共同提供阿霉素（DOX）和BCL 2的小干扰RNA（siRNA），以克服多药耐药（MDR），并通过联合化疗和RNA干扰（RNAi）治疗MCF-7/Adr癌细胞凋亡。采用低分子量分支PEI偶联羟丙基-β-环糊精（HP-β-CD）和叶酸（FA），形成共递送纳米载体（FA-HP-β-CD-PEI），利用空腔HP-β-CD包裹DOX，利用PEI的正电荷结合siRNA，实现肿瘤靶向共递送药物。载药纳米复合物（FA-HP-β-CD-PEI/DOX/siRNA）粒径分布均匀，细胞摄取率高，对BCL 2基因有明显的抑制作用，有望克服MDR，提高抗癌药物的疗效。此外，纳米复合物通过下调抗凋亡蛋白BCL 2的机制实现了显著的细胞凋亡，从而通过肿瘤靶向和RNA干扰提高了共同施用的DOX的治疗功效。我们的研究表明，使用我们的功能性共递送纳米载体联合RNAi治疗和化疗可以克服MDR并促进MDR癌细胞的凋亡，从而在治疗MDR癌症中具有潜在的应用前景。
Systemic administration of chemotherapy for cancer often faces drug resistance, limiting its applications in cancer therapy. In this study, we developed a simple multifunctional nanocarrier based on polyethylenimine (PEI) to codeliver doxorubicin (DOX) and BCL2 small interfering RNA (siRNA) for overcoming multidrug resistance (MDR) and enhancing apoptosis in MCF-7/Adr cancer cells by combining chemotherapy and RNA interference (RNAi) therapy. The low-molecular-weight branch PEI was used to conjugate hydroxypropyl-β-cyclodextrin (HP-β-CD) and folic acid (FA), forming the codelivery nanocarrier (FA-HP-β-CD-PEI) to encapsulate DOX with the cavity HP-β-CD and bind siRNA with the positive charge of PEI for tumor-targeting codelivering drugs. The drug-loaded nanocomplexes (FA-HP-β-CD-PEI/DOX/siRNA) showed uniform size distribution, high cellular uptake, and significant gene suppression of BCL2, displaying the potential of overcoming MDR for enhancing the effect of anticancer drugs. Furthermore, the nanocomplexes achieved significant cell apoptosis through a mechanism of downregulating the antiapoptotic protein BCL2, resulted in improving therapeutic efficacy of the coadministered DOX by tumor targeting and RNA interference. Our study indicated that combined RNAi therapy and chemotherapy using our functional codelivery nanocarrier could overcome MDR and enhance apoptosis in MDR cancer cells for a potential application in treating MDR cancers.