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

Abstract

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.

Keywords:

• codelivery
• gene silencing
• chemotherapy
• apoptosis
• tumor targeting

Acknowledgments

This work was supported by the National Natural Science Foundation of China (50830107, 20974129, U1032002, 81070349, 81071167), The Natural Science Foundation (9351027501000003) and S&T Programs (2009B030803003, 2010B031500011) of Guangdong Province, and the Guangzhou Scientific Project (2008Z1-D171).

Disclosure

The authors report no conflicts of interest in this work.