High-Entropy Alloy-Engineered ZnIn2S4 Photocatalyst for Efficient In Vitro Eradication of MRSA and Inhibition of Biofilm Formation via ROS-Mediated Mechanisms

Antibiotic-resistant bacterial infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), pose a critical clinical challenge and necessitate alternative non-antibiotic antimicrobial strategies. Herein, a high-entropy alloy-modified ZnIn2S4 (HEA–ZIS) photocatalytic nanoplatform was rationally engineered and evaluated for in vitro antibacterial performance. FeCoNiCuZn high-entropy alloy nanoparticles were uniformly anchored onto hierarchical ZnIn2S4 nanoflowers via a combined solvothermal–impregnation strategy. Structural and physicochemical characterizations reveal that the intrinsic flower-like morphology is well retained, while HEA incorporation induces lattice distortion, multivalent metal states, and interfacial charge redistribution. The optimized 3%HEA–ZIS exhibits potent antibacterial activity against MRSA under visible light, achieving 98.30% inactivation and a 5.91-log reduction, with a low minimum bactericidal concentration (0.30 mg mL−1). It also demonstrates strong antibiofilm activity by inhibiting MRSA biofilm formation, reducing biofilm biomass by over 84%, while maintaining good in vitro biosafety. Mechanistic studies reveal enhanced light absorption, improved charge separation, and accelerated interfacial electron transfer, promoting efficient oxygen activation. Electron paramagnetic resonance and in situ DRIFTS analyses identify a cascade reactive oxygen species (ROS) pathway responsible for the enhanced antibacterial efficacy. Overall, this work provides insights into high-entropy alloy-engineered semiconductor nanoplatforms and demonstrates their potential as promising biomedical nanomaterials for non-antibiotic antimicrobial applications.