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Reactive oxygen species (ROS) are a double-edged sword that possesses both beneficial and harmful effects. Although basic research on skin cancer prevention has undergone a huge transformation, cases of recurrence with higher rates of drug resistance are some of its drawbacks. Therefore, targeting mitochondria by ROS overproduction provides an alternate approach for anticancer therapy. In the present study, green-synthesized silver nanoparticles (AgNPs) were explored for triggering the ROS production in A431 skin carcinoma cells. The synthesized AgNPs were characterized for size, charge, morphology, and phase through high-throughput DLS, Fe-SEM, XRD, and ATR-FTIR techniques. Their physiochemical properties with hemoglobin and blood plasma were screened through hemolysis, hemagglutination assay, and circular dichroism spectroscopy confirmed their nontoxic nature. The AgNPs also exhibited additional efficacy in inhibiting biofilm produced by V. cholerae and B. subtilis, thereby facilitating better applicability in wound-healing biomaterials. The depolarization of mitochondrial membrane potential ΔΨm through excess ROS production was deduced to be the triggering force behind the apoptotic cell death mechanism of the skin carcinoma. Subsequent experimentation through DNA fragmentation, comet tail formation, cell membrane blebbing, and reduced invasiveness potentials through scratch assay confirmed the physiological hallmarks of apoptosis. Thus, depolarizing mitochondrial membrane potential through green-synthesized AgNPs provides an economic, nontoxic, specific approach for targeting skin carcinoma with additional benefits of antibacterial activities.

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