已发表论文

通过使用叶酸-聚乙烯亚胺共聚物羟丙基-β-环糊精 (cyclodextrin) 同时递送阿霉素 (doxorubicin) 和 Bcl-2 的 siRNA,使 MCF-7/ADR 细胞的发生多药耐药性逆转

 

Authors Li JM, Zhang W, Su H, Wang YY, Tan CP, Ji LN, Mao ZW

Published Date April 2015 Volume 2015:10 Pages 3147—3162

DOI http://dx.doi.org/10.2147/IJN.S67146

Received 2 May 2014, Accepted 9 June 2014, Published 23 April 2015

Abstract: 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.
Keywords: tumor targeting, codelivery, doxorubicin, BCL2 siRNA, overcome multidrug resistance