Concentration-dependent green synthesis of ZnO nanoparticles using Physalis angulata Linn. leaf extract: Structural evolution, cytocompatibility, and anti-Streptococcus mutans activity

Dental caries remains a major global oral health problem primarily associated with the biofilm-forming bacterium Streptococcus mutans . Conventional antimicrobial agents often exhibit limited biofilm penetration and may induce resistance, highlighting the need for sustainable nanomaterial-based alternatives with enhanced antibacterial efficacy and biocompatibility. In this study, zinc oxide nanoparticles (ZnONPs) were successfully synthesized via a green approach using Physalis angulata Linn. leaf extract as a multifunctional bioreductor and stabilizing agent. The novelty of this work lies in the first utilization of P. angulata leaf extract for concentration-dependent biosynthesis of ZnONPs integrated with comprehensive phytochemical profiling and biological evaluation. LC–HRMS analysis identified amino acids, organic acids, and nitrogen-containing metabolites that are likely involved in nanoparticle formation and stabilization. ZnONPs were synthesized using 15% and 25% extract concentrations and characterized by UV–Vis, FTIR, XRD, FESEM, TEM, EDX, and PSA–DLS analyses. The nanoparticles exhibited a highly crystalline hexagonal wurtzite structure with quasi-spherical morphology. Increasing extract concentration improved nanoparticle uniformity, colloidal stability, and surface functionalization while reducing particle size from approximately 23.65–42.77 nm to 16.99–29.90 nm. ZnONPs synthesized with 25% extract demonstrated superior antioxidant activity (IC₅₀ = 296.1 ppm), lower toxicity in the Brine Shrimp Lethality Test (IC₅₀ = 1.17 × 10⁵ ppm), and higher fibroblast viability (>88%). Both ZnONPs formulations completely inhibited S. mutans growth. Overall, P. angulata -mediated ZnONPs represent promising eco-friendly nanomaterials with excellent antibacterial activity, favorable biocompatibility, and potential applications in biomedical and oral antimicrobial therapies.