In vitro and in vivo evaluation of the efficacy of nanoformulation of siRNA as an adjuvant to improve the anticancer potential of cisplatin

Abstract

With the advent of advanced tools in molecular biology, understanding on cancer etiology has improved. siRNA can be considered as an effective tool in cancer therapy through silencing overexpressed genes responsible for cell proliferation or preventing apoptosis. However, some contentious issues such as stability and delivery of siRNA are to be resolved. Bcl-2, an anti-apoptotic gene, is overexpressed in a wide variety of cancers and responsible for drug resistance tumors. In our earlier studies, we developed a nanoformulation of siRNA targeting the Bcl-2 and achieved successful delivery in vitro and in vivo. To extend the scope of the study further, in the present work, we studied the role of nanoformulation of siRNA as adjuvant in chemotherapy with cisplatin. Dose dependant nephrotoxicity is a serious concern apart from other adverse effects of cisplatin. The IC50 value for cisplatin was decreased from 9.83μmol/l to 7.43μmol/l in HeLa cells and from 8.54μmol/l to 6.68μmol/l in HEp-2 cells, when it was given with siRNA nanoformulation. Cisplatin at the dose of 1.7mg/kg in combination with siRNA nanoformulation was effective in improving the lifespan of tumor bearing mice with significant decrease in nephrotoxicity.