Adriamycin-loaded Composite Micelles Reverse Drug Resistance In Cancer Cells And Its Mechanism

Objectives:Adriamycin-loaded composite micelles with high molecular material polyethylene glycol, polycaprolactone and Pluronic P105 or P85 were synthesized by using the solvent evaporation method. The inhibitory effect of adriamycin -loaded composite micelles and free adriamycin to the adriamycin-resistant human breast cancer cells MCF7/Adr and its parentalbreast cancer cells MCF7 was evaluated and its mechanism was investigated.Methods:We used the solvent evaporation method to synthesize PEG-PCL/P105 and PEG-PCL/P85 adriamycin-loaded composite micelles, and then measured concentration of adriamycin in the composite micellesby ultraviolet spectrophotometer. The inhibitory effect of doxorubicin-loaded composite micelles and free adriamycin to the adriamycin-resistant human breast cancer cells MCF7/Adr and its parental breast cancer cells MCF7 was evaluated by a standard MTT assay. The confocal laser scanning microscopy (CLSM) was applied to determine the intake and retention of the drug in the cells. The expression changes of multi-drug resistance protein P-glycoprotein (P-GP), multi-drug resistance associated protein 1 (MRP1), and breast cancer resistance protein (BCRP) was measured by western blot and RT-PCR.Results:compared with free Adriamycin, adriamycin -loaded composite micelles increased the cellular uptake in the MCF7/Adr cells, and showed longer intracellular retention. Adriamycin -loaded composite micelles also reduced the expression of MRP1,when compared with free adriamycin, and show greater inhibitory effect in the MCF7/Adr cells. However, there were no differences in the MCF7 cells.Conclusion:PEG-PCL/P105 and PEG-PCL/P85 doxorubicin-loaded composite micelles can reverse the drug resistance of MCF7/Adr cells. Micelles allow the MCF7/Adr cells a greater ability to uptake and retain the adriamycin, and decrease the expression of protein MRP1.