The efficacy of WGA modified daunorubicin anti-resistant liposomes in treatment of drug-resistant MCF-7 breast cancer

Abstract

Background: Breast cancer is the most common malignancy and remains a leading cause of cancer-related deaths in female. Chemotherapy failure of breast cancer is mainly associated with multidrug resistance of cancer cells.Purpose: The WGA modified daunorubicin anti-resistant liposomes were developed for circumventing the multidrug resistance and eliminating cancer cells.Methods: WGA was modified on liposomal surface for increasing the intracellular uptake. Tetrandrine was inserted into the phospholipid bilayer for reversing cancer drug-resistance, and daunorubicin was encapsulated in liposomal aqueous core as an anticancer agent. Evaluations were performed on MCF-7 cells, MCF-7/ADR cells and xenografts of MCF-7/ADR cells.Results: In vitro results showed that WGA modified daunorubicin anti-resistant liposomes exhibited suitable physicochemical properties, significantly increased intracellular uptake in both MCF-7 cells and MCF-7/ADR cells, and circumvented the multidrug resistance via inhibiting P-gp. In vivo results demonstrated that the targeting liposomes showed a long-circulatory effect in blood system, and could remarkably accumulate at the tumor location. The involved action mechanisms for the enhanced anticancer efficacy were activation of pro-apoptotic proteins (Bax and Bok), apoptotic enzymes (caspase 8, caspase 9 and caspase 3).Conclusion: The established WGA modified daunorubicin anti-resistant liposomes could provide a potential strategy for treating resistant MCF-7 breast cancer.