Enhanced antitumor activity of epigallocatechin gallate-conjugated dual-drug-loaded polystyrene-polysoyaoil-diethanol amine nanoparticles for breast cancer therapy

The development of novel combination anticancer drug delivery systems is an important step to improve the effectiveness of anticancer treatment in metastatic breast cancer and to overcome increased toxicity of the currently used combination treatments. The aim of this study was to assess efficient targeting, therapeutic efficacy, and bioavailability of a combination of drugs (curcumin and -tocopheryl succinate) loaded polystyrene-polysoyaoil-diethanol amine nanoparticles. Polystyrene-polysoyaoil-diethanol amine nanoparticles encapsulating two drugs, individually or in combination, were prepared by double-emulsion solvent evaporation method, resulting in particle size smaller than 250nm with a surface negative charge between -30 and -40mV. Entrapment efficiency of curcumin and -tocopheryl succinate in the epigallocatechin gallate-conjugated dual-drug-loaded nanoparticles was found to be 68% and 80%, respectively. The release kinetics of curcumin and -tocopheryl succinate from the nanoparticles exhibited a gradual and continuous profile followed by an initial burst behavior with a release over 20days in vitro. Next, we have investigated the anticancer activity of nanoparticles encapsulating both the drugs and individually drug in human breast cancer cells (MDA-MB-231) using double-staining-based cell death analysis, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assessment of cytotoxicity and flow cytometer. In vitro cytotoxicity studies revealed that epigallocatechin gallate--tocopheryl succinate/curcumin-polystyrene-polysoyaoil-diethanol amine nanoparticles are more potent than the corresponding -tocopheryl succinate/curcumin-polystyrene-polysoyaoil-diethanol amine nanoparticles and their single-drug-loaded forms and show a synergistic and breast tumor targeting function. Thus, here, we propose epigallocatechin gallate-conjugated curcumin and -tocopheryl succinate-loaded polystyrene-polysoyaoil-diethanol amine nanoparticles which effectively inhibit tumor growth and reduce toxicity compared to single-drug chemotherapy.