Rational Design of Copper‐Based Metallic Nano‐Antibiotic against Drug‐Resistant Bacteria Infection

Abstract The rapidly increasing global incidence of antibiotic‐resistant bacterial infections poses a serious threat to public health worldwide, demanding immediate development of novel antimicrobial approaches. In this study, a rationally designed multifunctional metallic nano‐antibiotic (MNAB) system using an in‐situ reduction method is developed. The strategic incorporation of cuprous species substantially enhanced antimicrobial activity against clinically isolated strains, including two Gram‐positive and four Gram‐negative bacterial species. Remarkably, the system exhibited minimum inhibitory concentrations (MIC) of ≈20 ppm for Gram‐positive bacteria and ≈60 ppm for Gram‐negative bacteria, demonstrating efficacy on par with conventional antibiotics. Mechanistic investigations revealed that MNABs exert their antimicrobial effects through potent oxidative damage to cellular membranes while simultaneously modulating multiple gene clusters, confirming their broad‐spectrum antimicrobial capabilities. This study provides a strategic blueprint for developing next‐generation antibiotic alternatives, offering a promising solution for combating drug‐resistant bacterial infections.