Biogenically synthesized zinc oxide nanoparticles using Penicillium chrysogenum filter to combat methicillin-resistant Staphylococcus aureus (MRSA) and Cancer Cells

Staphylococcus aureus is a major opportunistic pathogen that persistently colonizes approximately 20% of the human population. It is capable of causing diverse infections ranging from mild skin lesions to severe, life-threatening conditions. The emergence of methicillin-resistant S. aureus (MRSA) has complicated treatment strategies and intensified the search for alternative antimicrobial agents. This study presents a novel, eco-friendly biosynthesis of zinc oxide nanoparticles (ZnO-NPs) using the cell-free filtrate of Penicillium chrysogenum and investigates their antibacterial, anti-virulence, antioxidant, and anticancer activities. The synthesized ZnO-NPs were characterized using UV-Visible spectroscopy, high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), zeta potential and X-ray diffraction (XRD). Antibacterial efficacy was determined against MRSA isolates through MIC assays, while biofilm inhibition and virulence gene expression analyses were performed to assess anti-virulence activity. Antioxidant capacity was evaluated using DPPH and ABTS assays, and cytotoxicity against HepG2 and MCF-7 cancer cell lines was assessed using MTT assays. UV-Vis spectra exhibited a distinct absorption peak at 430 nm. HR-TEM analysis revealed predominantly spherical to slightly irregular ZnO-NPs with an average diameter of 43.17 nm (ranging 50-70.25 nm). The biosynthesized ZnO-NPs demonstrated strong antibacterial activity against MRSA, with MIC values between 125 and 250 µg/mL, and significantly inhibited biofilm formation. Moreover, they downregulated key virulence genes by 2.0 - 4.6-fold. The nanoparticles also exhibited notable antioxidant activity with IC₅₀ values of 205 µg/mL (DPPH) and 315 µg/mL (ABTS), as well as potent anticancer effects with IC₅₀ values of 13.74 ± 0.02 µg/mL (HepG2) and 19.12 ± 0.51 µg/mL (MCF-7). This study demonstrates, for the first time, the biosynthesis of ZnO-NPs using P. chrysogenum filtrate with multi-functional bioactivity, including antibacterial, anti-virulence, antioxidant, and anticancer properties. These findings highlight the potential application of biosynthesized ZnO-NPs as promising biocompatible agents for combating MRSA infections and certain cancer types, paving the way for sustainable nanotherapeutic development