Control of Solid Tumor Growth in Mice Using EGF Receptor-Targeted RNA Replicase-Based Plasmid DNA

Abstract

Previously, it was shown that treatment of tumor-bearing mice with an RNA replicase-based plasmid that produces dsRNA when transfected into tumor cells significantly inhibited the tumor growth. In the present study, the feasibility of further improving the anti-tumor activity of the RNA replicase-based plasmid by targeting it into tumors cells was evaluated. An EGF-conjugated, polyethylene glycosylated cationic liposome was developed to deliver the RNA replicase-based plasmid, pSIN-β, into EGF receptor-overexpressing human breast cancer cells (MDA-MB-468) in vitro and in vivo. Delivery of pSIN-β using the EGF receptor-targeted liposome more effectively controlled the growth of MDA-MB-468 tumors (and human epidermoid carcinoma A431 tumors) in mice than using untargeted liposome. The pSIN-β carried by the EGF receptor-targeted liposome caused the complete regression of MDA-MB-468 tumors in mice, probably due to the enhancement of its proapoptotic, antiproliferative and antiangiogenic activities. Tumor-targeted RNA replicase-based plasmids hold a strong potential in tumor therapy.