Targeted-delivery of siRNA via a polypeptide-modified liposome for the treatment of gp96 over-expressed breast cancer

Abstract

Targeted gene therapy has led to significant breakthroughs in cancer treatment. Heat shock protein gp96 is an emerging target for tumor treatment because of its transfer ability from reticulum to tumor cell surface. CDO14 is a peptide cationic liposome developed in our laboratory with higher gene transfection efficiency and lower toxicity compared with the existing cationic liposomes. In this study, gp96-targeted liposome p37-CDO14 was constructed by modifying cationic liposome CDO14 with a gp96 inhibitor, helical polypeptide p37. Liposome p37-CDO14 could specifically bind to breast cancer cells with gp96-overexpression on the cell membrane. Both liposomes CDO14 and p37-CDO14 showed high delivery efficiency for survivin siRNA (siSuvi) to SK-BR-3 and MCF-7 cells via obviously decreased survivin expression level and cell viability. P37-CDO14 significantly increased the accumulation of FAM-siRNA in tumor compared with CDO14. SiSuvi transfected by CDO14 and p37-CDO14 could inhibit the growth of xenograft in mice and the expression of survivin in tumor tissues. The anti-tumor effect of siSuvi delivered by p37-CDO14 was much higher than that delivered by CDO14. This suggests that targeted liposome p37-CDO14 is a potential gene vector for the therapy of gp96 overexpressed breast cancer.

Keywords: Breast cancer; Polypeptide p37; Survivin siRNA; Targeted liposome; gp96.