Liposomes co-delivery system of doxorubicin and astragaloside IV co-modified by folate ligand and octa-arginine polypeptide for anti-breast cancer.

Abstract

Doxorubicin (DOX) is one of the core drugs in triple-negative breast cancer (TNBC) chemotherapy, but its resistance has severely limited its clinical application. Our previous study found that astragaloside IV (AS-IV) has a good reversal effect on doxorubicin resistance. In order to encapsulate DOX and AS-IV simultaneously, a new liposome-targeted co-delivery system co-modified by the folate ligand (FA) and octa-arginine polypeptide (R8) (FA-R8-LPs, for short) was prepared. In this co-delivery system, R8 not only served as a bond connecting the FA to the liposome, but also played the role of cell penetrating peptides (CPPs). This design effectively increased the tumor targeting and cellular uptake capacity of liposomes. The results of the cytotoxicity test indicated that FA-R8-LPs significantly inhibited the proliferation of the DOX resistant cell line MDA-MB-231/DOX in vitro. In nude mice tumor models inoculated with MDA-MB-231/DOX cells, FA-R8-LPs significantly inhibited tumor growth, and overcame doxorubicin resistance, exhibiting excellent antitumor effects. This study demonstrates that liposome-targeted co-delivery systems based on FA and R8 double modifying may provide a new and effective strategy for the treatment of TNBC, which is of great significance for drug combination.