PEGylated Doxorubicin Micelles Loaded with Curcumin Exerting Synergic Effects on Multidrug Resistant Tumor Cells

A novel folate-polyethylene glycol-succinic acid-doxorubicin conjugate (FA-PEG-SA-DOX) micelle loaded with curcumin (CUR) is designed and prepared to target tumor cells via folate-folate receptor interactions and co-deliver chemotherapeutic agent DOX and chemosensitizer CUR for treatment of multidrug resistant human breast cancer MCF-7/ADR cells. The CUR/FA-PEG-SA-DOX micelles are characterized with the average size of 90.64 +/- 0.15 nm and the zeta potential of -15.3 +/- 0.8 mV. The CUR and DOX contents of the micelles are 12.07 and 15.69% (w/w), respectively. The cytotoxicity, cellular uptake and efflux of the micelles are investigated by using MCF-7/ADR cells. The results demonstrate that the CUR/FA-PEG-SA-DOX micelles have greater toxicity (IC50 = 3.10 mu g/ml) compared to the free DOX (IC50 = 31.99 mu g/ml), moreover, the micelles present increased cellular uptake and reduced cellular efflux. The combination index of CUR/FA-PEG-SA-DOX micelles was 0.17, which indicate a strong synergistic antitumor efficacy against MCF-7/ADR cells. These results suggest that Curcumin-loaded FA-PEG-SA-DOX micelles may be a promising nanomedicine for co-delivery dual-drug treatment for cancer.