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-β, into EGF receptor-overexpressing human breast cancer cells (MDA-MB-468) in vitro and in vivo.

RESULTS:

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.

DISCUSSION:

Tumor-targeted RNA replicase-based plasmids hold a strong potential in tumor therapy.

• Authors: B Leticia Rodriguez, Xinran Li, Kaoru Kiguchi, John DiGiovanni, Evan C Unger, Zhengrong Cui
• Journal: Nanomedicine (London, England) (Nanomedicine (Lond)) Vol. 7 Issue 4 Pg. 475-91 (Apr 2012) ISSN: 1748-6963 [Electronic] England
• PMID: 22296186 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Liposomes
• Polyethylene Glycols
• DNA
• ErbB Receptors
• RNA-Dependent RNA Polymerase

Topics

• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (genetics, therapy)
• DNA (genetics)
• ErbB Receptors (genetics)
• Female
• Humans
• Liposomes (chemistry)
• Mice
• Mice, Nude
• Microscopy, Fluorescence
• Plasmids (genetics)
• Polyethylene Glycols (chemistry)
• RNA-Dependent RNA Polymerase (genetics)