Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of Adriamycin in a gold nanoshell-based drug/gene co-delivery system

Abstract

// Li Ding 1, * , Ruonan Sun 1, * , Xinyue Zhang 1, 2, 3, 4, 5 1 College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu 225009, China 2 Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China 3 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China 4 Jiangsu Key Laboratory of Zoonosis, Yangzhou, Jiangsu 225009, China 5 Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, Jiangsu 225009, China * These authors have contributed equally to this work Correspondence to: Xinyue Zhang, email: xyzhang_1@163.com Keywords: Rap2b, siRNA, Adriamycin, gold nanoshells, cancer therapy Received: December 14, 2016      Accepted: February 07, 2017      Published: February 19, 2017 ABSTRACT Rap2b is a novel p53 target we have identified recently. Knockdown of Rap2b sensitizes HCT116 cells to adriamycin-induced apoptosis, indicating that Rap2b promotes adriamycin resistance in cancer cells. In the present study, we designed a nanostructure-based drug/gene delivery system to evaluate the potential of Rap2b siRNA as a therapeutic agent against human cancers. Specifically, after co-incubated with HCT116 cells, adriamycin- and Rap2b siRNA-loaded gold nanoshells were internalized. Subsequent laser irradiation promoted release of adriamycin and Rap2b siRNA from the nanoparticles. The laser-induced release of Rap2b siRNA decreased cellular expression of Rap2b and significantly enhanced the anticancer therapeutic efficacy of adriamycin in vitro and in vivo . In addition, laser irradiation of the nanoparticles might exert an additional thermal killing effect on cancer cells and further improved the anticancer efficacy of adriamycin. In summary, Rap2b siRNA is a potential enhancing agent for adriamycin-based anticancer therapeutics and the gold nanoshell-based drug/gene delivery system carrying both adriamycin and Rap2b siRNA provides a promising anticancer therapeutic strategy.