Folic Acid—Targeted Doxorubicin Drug Delivery System for Triple-Negative Breast Cancer Treatment

Triple-negative breast cancer (TNBC) is a highly aggressive type of cancer with limited therapeutic options. However, this type of cancer cells has shown overexpression of folate receptors, which bind with folic acid (FA) with high affinity. This feature can be used for targeting of nanocarriers, such as liposomes. In order to further examine the potential of increased efficacy by targeting the folate receptor, we prepared folate conjugated liposomes (DSPC/Chol/PEG/DSPE-PEG-FA) and loaded them with doxorubicin (DOX), an anticancer drug. For this, we first synthesized and verified the conjugate between FA and PEG-lipid (FA-PEG-lipid). After that, liposomes were prepared with thin film hydration method followed by probe sonication. Three different types of targeted liposomes having different concentrations of FA-PEG-lipid in their membranes (0.1 mol%, 0.5 mol%, and 1 mol%) were evaluated for their cytotoxicity (DOX-loaded liposomes) on MDA-MB-231 (epithelial human breast cancer cells), 4T1 (murine mammary carcinoma cells), and MCF7 (Human breast cancer cells); the two first are TNBC cells and overexpress FA receptor, the third does not. Cytotoxicity results proved that increasing amounts of FA on the surface of liposomes results in enhanced antitumor activity of liposomal-DOX in the case of the cancer cells, which overexpress the FA receptor.