Control of solid tumor growth in mice using EGF receptor-targeted RNA replicase-based plasmid DNA.

ABSTRACT

AIM: 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. MATERIAL & METHODS: An EGF-conjugated, polyethylene glycosylated cationic liposome was developed to deliver the RNA replicase-based plasmid, pSIN-ß, into EGF receptor-overexpressing human breast cancer cells (MDA-MB-468) in vitro and in vivo. RESULTS: Delivery of pSIN-ß 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-ß 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. DISCUSSION: Tumor-targeted RNA replicase-based plasmids hold a strong potential in tumor therapy.