Functional and NanotherapeuticPotential of Fungal-mediated Zinc OxideNanoparticles in Melanoma Cells

Abstract

Background: Melanoma is a treatment-resistant malignancy characterized by rapid metastatic progression and
therapeutic resistance, highlighting the need for alternative treatment strategies. Fungal-mediated green synthesis
of zinc oxide nanoparticles (ZnO NPs) offers a potentially biocompatible and sustainable approach with anticancer
activity. Aim: To synthesize and characterize fungal-mediated zinc oxide nanoparticles (ZnO NPs) and evaluate
their cytotoxic and mechanistic effects against A375 human melanoma cells. Materials and Methods: Fungal-
mediated ZnO NPs were characterized using Fourier transform infrared spectroscopy and scanning electron
microscopy. Cytotoxicity against A375 melanoma cells was assessed by MTT assay, while morphological and
apoptotic changes and associated molecular signaling pathways were evaluated. Results: The ZnO NPs had an
average particle size of 32.6 nm and showed an IC₅₀ of 6 ± 0.2 μg/mL at 24 h. Treatment induced apoptotic changes,
reactive oxygen species generation, mitochondrial dysfunction, caspase activation, increased Bax expression,
and reduced Bcl-2 expression. PI3K/Akt/mTOR and NF-κB signaling were also inhibited. Conclusion: Fungal-
mediated ZnO NPs demonstrate promising anti-melanoma activity through induction of intrinsic apoptosis and
suppression of prosurvival signaling pathways, although in vivo and clinical validation is required.