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

Seyin Zou,^1,3,† Nuo Cao,^1,† Du Cheng,² Rongqin Zheng,⁴ Jin Wang,⁴ Kangshun Zhu,⁴ Xintao Shuai^1,2

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 work

Abstract: 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