VEGF siRNA delivered by polycation liposome-encapsulated calcium phosphate nanoparticles for tumor angiogenesis inhibition in breast cancer

Abstract

Jinliang Chen,1 Xiaoyi Sun,2 Rong Shao,1 Yichao Xu,1 Jianqing Gao,3 Wenquan Liang3 1Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, 2Department of Pharmacy, Zhejiang University City College, 3Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Abstract: Angiogenesis plays an important role in tumor development and metastasis, and many cancer cells upregulate VEGF expression to promote angiogenesis. Silencing VEGF expression by RNA interference is expected to be a promising strategy to suppress the tumor growth. However, low transfection efficiency and instability are the main barriers for small interfering RNA (siRNA) delivery. In this study, we developed polycation liposome-encapsulated calcium phosphate nanoparticles (PLCP) for siRNA delivery in vivo. VEGF expression silencing effect in MCF-7 cells was investigated by real-time quantitative polymerase chain reaction and Western blot assay. VEGF siRNA mediated by PLCP can reduce 60%–80% VEGF expression in vitro, which was significantly higher than that mediated by Lipofectamine 2000. Furthermore, significant tumor growth and angiogenesis inhibition were observed in MCF-7 xenografts mice when treated with PLCP/VEGF siRNA or combined with doxorubicin. In conclusion, the combination of silencing VEGF expression and chemotherapeutics would be a potential treatment for cancer therapy. Keywords: polycation liposomes, calcium phosphate nanoparticles, VEGF, siRNA, angiogenesis inhibition 

Keywords

• polycation liposomes
• calcium phosphate nanoparticles
• VEGF
• siRNA
• angiogenesis inhibition