Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Abstract

Seyin Zou,1,3,† Nuo Cao,1,† Du Cheng,2 Rongqin Zheng,4 Jin Wang,4 Kangshun Zhu,4 Xintao Shuai1,2 1Center of Biomedical Engineering, Zhongshan School of Medicine, 2PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, 3Department of Laboratory Medicine,The Third Affiliated Hospital, Guangzhou Medical University, 4The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China †These authors contributed equally to this workAbstract: A folate conjugated ternary copolymer, FA–PEG–PEI–PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ε-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.Keywords: codelivery, gene silencing, chemotherapy, apoptosis, tumor targeting