Bioflavonoid Fisetin Loaded α-Tocopherol-Poly(lactic acid)-Based Polymeric Micelles for Enhanced Anticancer Efficacy in Breast Cancers.

In this study, tocopherol based polymeric micelles were successfully prepared to enhance the anticancer effect of fisetin (FIS) in breast cancer cells.

The drug-loaded carrier was characterized in terms of physicochemical and in vivo parameters.

Compared to FIS, FIS-TPN showed higher cellular uptake in MCF-7 breast cancer cells as revealed by CLSM and flow cytometry. The cytotoxicity assay results clearly showed that the free FIS and FIS-TPN exhibited a typical dose-dependent toxic effect in MCF-7 breast cancer cells. Especially, enhanced cytotoxic effect of FIS was observed when loaded in a nanocarrier. Free FIS induced a ~11% apoptosis whereas FIS-TPN induced a significantly greater apoptosis of ~20% by the end of 24 h. At 48 h, similar trend continued and free FIS showed ~30% of apoptosis whereas ~42% cell apoptosis was observed in FIS-TPN treated group. Notably, migration of cancer cell was significantly inhibited when treated with FIS-TPN formulations. The FIS-TPN significantly reduced to tumor burden and H&E staining showed the lowest tumor volume and higher cell apoptosis.

All the findings suggest that the fisetin-loaded TPGS-PLA polymeric micelles serve as a potential candidate and promising alternative for the effective treatment of breast cancers.