ABSTRACT
Codelivery of chemo-sensitizers with chemotherapeutics using combo nanomedicine is a promising platform for overcoming chemoresistance in breast cancer. However, tumor accumulation of nano-carriers based on enhanced permeability and retention (EPR) effect is confounded by heterogeneity in tumor microenvironment. Adsorption of protein corona on surface of nanoparticle boost up clearance by reticulo-endothelial system. In this study, a surface functionalized magnetic nanocomposite (NC) for codelivery of doxorubicin (DOX) and curcumin (CUR) is developed. NCs were coated with hydroxyapatite and were also cross linked with ß-cyclodextrin. NCs efficiently encapsulated DOX and CUR. Release of CUR and DOX were in a sustained pH-depended pattern. ß-cyclodextrin functionalization reduced protein corona according sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. As shown by flowcytometric and confocal microscopy analyses, NCs internalized efficiently by human breast carcinoma cells MCF-7 and adriamycin resistant MCF-7 (MCF-7/adr) cells. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test demonstrated superior cytotoxicity of DOX-CUR loaded NCs. Anti-tumor efficacy analyses confirmed reduction in relative tumor volume size (RTV%) compared to control group. Western blot analyses demonstrated marginal CUR mediated P-glycoprotein (P-gp) down regulation. DOX-CUR loaded NCs efficiently accumulated into the tumor via external magnet guidance. Nevertheless, the increased tumor accumulation did not correlate with pharmacologic responses such as RTV% and significant superiority over free DOX was not observed.
