Preparation of DSPE-PEG-cRGD Modified Cationic Liposomes for Delivery of OC-2 shRNA and The Antitumor Effects on Breast Cancer.

Cationic liposome delivery of interfering RNA (shRNA) plays an important role in tumor therapy. The cyclic Arg-Gly-Asp (cRGD) modified cationic liposomes (cRGD-CL) were designed for targeted delivery of ONECUT2 (OC-2) shRNA (pshOC-2) to breast cancer cells. The characterization analysis of cationic liposome showed that the prepared cRGD-CL/pshOC-2 lipoplexes had uniform particle size (150 ± 1.02 nm), moderate zeta potential (19.8 ± 0.249 mV) and high encapsulation efficiency (up to 96%). The results of flow cytometer showed that the introduction of cRGD could significantly promote the liposomes targeting tumor cells. In MCF-7 cells, the pshOC-2 could down-regulate expression of OC-2 and result in cell apoptosis, inhibition of the wound healing, migration and cell colony formation, in which the signal pathways of Bcl-xL, Bcl-2 were inhibited and the signal pathways of Bax and Cleaved Caspase-3 were promoted. In MCF-7 xenograft mice, intravenous administration of cRGD-CL/pshOC-2 lipoplexes could effectively reduce the expression of OC-2 in tumors and result in apparently antitumor effects, which suggested that the lipoplexes might be deeply penetrated into tumor through receptor-mediated transcytosis. The results revealed that the cationic liposome (cRGD-CL) was an effective delivery system for OC-2 shRNA, which might be an effective therapeutic candidate for breast cancer.