Multifunctional selenium nanoparticles as carriers of HSP70 siRNA to induce apoptosis of HepG2 cells

Abstract

Yinghua Li,1 Zhengfang Lin,1 Mingqi Zhao,1 Tiantian Xu,1 Changbing Wang,1 Huimin Xia,1,* Hanzhong Wang,2,* Bing Zhu1,* 1Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 2State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People’s Republic of China *These authors contributed equally to this work Abstract: Small interfering RNA (siRNA) as a new therapeutic modality holds promise for cancer treatment, but it is unable to cross cell membrane. To overcome this limitation, nanotechnology has been proposed for mediation of siRNA transfection. Selenium (Se) is a vital dietary trace element for mammalian life and plays an essential role in the growth and functioning of humans. As a novel Se species, Se nanoparticles have attracted more and more attention for their higher anticancer efficacy. In the present study, siRNAs with polyethylenimine (PEI)-modified Se nanoparticles (Se@PEI@siRNA) have been demonstrated to enhance the apoptosis of HepG2 cells. Heat shock protein (HSP)-70 is overexpressed in many types of human cancer and plays a significant role in several biological processes including the regulation of apoptosis. The objective of this study was to silence inducible HSP70 and promote the apoptosis of Se-induced HepG2 cells. Se@PEI@siRNA were successfully prepared and characterized by various microscopic methods. Se@PEI@siRNA showed satisfactory size distribution, high stability, and selectivity between cancer and normal cells. The cytotoxicity of Se@PEI@siRNA was lower for normal cells than tumor cells, indicating that these compounds may have fewer side effects. The gene-silencing efficiency of Se@PEI@siRNA was significantly much higher than Lipofectamine 2000@siRNA and resulted in a significantly reduced HSP70 mRNA and protein expression in cancer cells. When the expression of HSP70 was diminished, the function of cell protection was also removed and cancer cells became more sensitive to Se@PEI@siRNA. Moreover, Se@PEI@siRNA exhibited enhanced cytotoxic effects on cancer cells and triggered intracellular reactive oxygen species, and the signaling pathways of p53 and AKT were activated to advance cell apoptosis. Taken together, this study provides a strategy for the design of an anticancer nanosystem as a carrier of HSP70 siRNA to achieve synergistic cancer therapy. Keywords: selenium nanoparticles, siRNA, polyethylenimine, reactive oxygen species, apoptosis, anticancer

Keywords

• Selenium nanoparticles
• siRNA
• Polyethylenimine
• Reactive oxygen species
• apoptosis