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Folic Acid – targeted Doxorubicin drug delivery system for triple-negative breast cancer treatment.
1, 2 , 2, 3 , 1, 2 , 1, 2 , 1, 2 , * 1, 2
1  Foundation for Research and Technology Hellas, Institute of Chemical Engineering Sciences, FORTH/ICE-HT, Rio-Patras 26504, Greece
2  Lab. Pharm. Technology, Department of Pharmacy, University of Patras, Rio-Patras 26504, Greece
3  Foundation for Research and Technology Hellas, Institute of Chemical Engineering Sciences, FORTH/ICE-HT, Rio-Patras 26504

Abstract:

Triple-negative breast cancer (TNBC) is a highly aggressive type of cancer with limited therapeutic options. However, this type of cancer cells have shown overexpression of folate receptors, which bind with folic acid (FA) with high affinity. This feature can be used for therapeutic targeting in combination with 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 were evaluated having concentrations of FA-PEG-Lipid in their membranes (0.1 mol%, 0.5 mol% and 1mol%). The various formulations were evaluated for their uptake (FITC-dextran encapsulating liposomes) and for their cytotoxicity (DOX-loaded liposomes) using three different cancer cell lines, 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 the third is not. Cellular uptake results proved that increasing amounts of FA on the surface of liposomes results in enhance uptake by TNBC cells. Furthermore, the antitumor activity of liposomal-DOX was significantly increase by folate conjugation on their surface, especially in the case of the TNBC cancer cells.

Keywords: liposomes ; folic acid ; doxorubicin ; breast cancer ; TNBC
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