Cell Death Mechanisms Induced by Green Synthesized Silver Nanoparticles in Combination with Pheophorbide-a Mediated Photodynamic Therapy Against Resistant MCF-7 Cells Overexpressed with P-Glycoprotein

Globally, multidrug resistance (MDR) in breast cancer has become the major cause of morbidity and mortality among women. This study was designed to overcome resistance, reduce dose-dependence in photodynamic therapy (PDT) and evaluate cell death mechanisms induced by green synthesized silver nanoparticles (AgNPs) in combination with pheophorbide-a mediated PDT on superlative, and most architectured three-dimensional (3-D) doxorubicin (DOX) resistant MCF-7 breast cancer cells with overexpressed p-glycoproteins in vitro. In addition to the aforementioned scope, the combination of green NPs with PDT has been reported to yield a good disease prognosis which in most cases is accompanied with manageable adverse effects. Briefly, MDR MCF-7 breast cancer cells were cultured in a 96 well plate to form 3D tumor spheroids and later treated with optimized concentrations of AgNPs and pheophorbide-a in monotherapy. After 24 h treatment, 3-[4,5-dimethylthiazole-2- yl]-2,5- diphenyl tetrazolium bromide (MTT) assay was performed to determine the 50% inhibitory concentration (IC50) for both experimental models. Morphological changes were observed by using an inverted light microscope, viability by MTT assay, and cell death analysis by Annexin V-FITC-PI staining. Taken together, the results from this study displayed a dose-dependent decrease in cell viability which was accompanied by significant morphological changes. Furthermore, Annexin V-FITC-PI assay showed apoptosis as the most prominent cell death mechanism induced by PPBa-mediated PDT and AgNPs. Taken together, the findings from the present study highlight the advantages of green nanotechnology in cancer therapy.