Rap2b siRNA significantly enhances the anticancer therapeutic efficacy of Adriamycin in a gold nanoshell-based drug/gene co-delivery system
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Li Ding1,*, Ruonan Sun1,*, Xinyue Zhang1,2,3,4,5
1College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, Jiangsu 225009, China
2Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China
3Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225009, China
4Jiangsu Key Laboratory of Zoonosis, Yangzhou, Jiangsu 225009, China
5Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou University, Yangzhou, Jiangsu 225009, China
*These authors have contributed equally to this work
Xinyue Zhang, email: [email protected]
Keywords: Rap2b, siRNA, Adriamycin, gold nanoshells, cancer therapy
Received: December 14, 2016 Accepted: February 07, 2017 Published: February 19, 2017
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.
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