Green Synthesis of Silver Nanoparticles Using Musa balbisiana and Their Cytotoxic Effect on HL-60 and SiHa Cancer Cells Through Clathrin-Mediated Endocytosis

We report herein a one-step, biomimetic synthesis of silver nanoparticles (AgNPs) from Musa balbisiana leaf extract having a cytotoxic effect on SiHa and HL-60 cancer cell lines without affecting non-cancerous, healthy peripheral blood mononuclear cells (PBMCs). The EDX analysis of AgNP dispersion, with a peak of 3.2 keV, confirmed the presence of elemental silver with a weight percentage of 54.57%. As is revealed from both SEM and TEM, monodispersed AgNPs were spherical in morphology with a diameter ranging from 11.28 to 87.53 nm with an average size of 12 nm. The diffraction pattern revealed polycrystalline AgNPs with FCC crystal structure. We report increased cytotoxicity accompanied with characteristic morphological change in HL-60 and SiHa, significant reduction in proliferation, increased reactive oxygen species (ROS) generation, and decreased mitochondrial membrane potential (MMP) following AgNP treatment at various doses. No such detrimental cellular impact of AgNPs was observed on healthy PBMCs. Fluorescence microscopy tracked coumarin-loaded AgNP accumulation in lysosomes as well as the nucleus, suggesting that both lysosome and nucleus served as cellular targets of AgNPs. AgNPs were internalized through passive and active pathways and that energy-dependent, clathrin-mediated endocytosis was involved in the trafficking of AgNPs. Our in silico docking studies confirm the binding of AgNPs to adaptor protein 2 on the β2 subunit facilitating clathrin-mediated endocytosis. Graphical abstract