Synergic anticancer effects of morin hydrate and sorafenib delivered via polymeric iron oxide nanoparticles for the treatment of triple-negative breast cancer.

A magnetic codelivery method using morin hydrate (MH) and sorafenib (SF) was used to control cancer recurrence in human triple-negative breast cancer (TNBC). Combined with anticancer drugs, SF and MH showed synergistic effects in TNBC treatment. Nevertheless, their dissimilar polarities make co-encapsulation using traditional delivery methods challenging. Hence, in this study, MH-, SF-loaded zein (ZN)-, and chitosan (CS)-coated iron oxide (Fe3O4) (termed MH-SF/ZN@CS/Fe3O4) were developed via layer-by-layer deposition and anti-solvent precipitation to overcome these problems and increase therapeutic efficacy. Nanoparticles with an average diameter of 20 nm were fabricated. Approximately 18% and 16% of SF and MH drug-loading contents were present, respectively. An intriguing degree of pH sensitivity was observed, with SF and MH release from MH-SF/ZN@CS/Fe3O4 faster at pH 6.5 than at pH 7.4. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that MH/SF-loaded magnetic polymeric nanoparticles displayed considerable synergistic in vitro cytotoxicity against MDA-MB-231 TNBC cells compared to other groups. Cell morphology and apoptosis mechanism were investigated, showing that MH-SF/ZN@CS/Fe3O4 induced apoptosis in MDA-MB-231 cancer cells. Morphological investigation of cancer cells was conducted via biochemical analysis, and the apoptotic mechanism of the cells was examined using flow cytometry with Annexin V-fluorescein isothiocyanate and propidium iodide. These findings indicate the potential of dual-drug-loaded magnetic polymeric nanoparticles for targeting cancer cells.