Abstract

The escalating incidence of antibacterial resistance presents a formidable challenge in managing bacterial infections. Traditional Zn-based antibacterial agents face limitations due to their reliance on ultraviolet activation and potential neurotoxicity. The combination of nanotechnology and traditional Chinese medicine (TCM) not only reduces the side effects of Zn 2+ but also enhances therapeutic efficacy. In this study, we synthesized Zn-baicalein nanoparticles (Zn-BE NPs) that self-assemble through chemical coordination, offering broad-spectrum antibacterial capabilities. The Zn component exhibited inherent antibacterial properties by disrupting the synthesis of bacterial metabolic enzymes and destroying genetic factors. Baicalein (BE), derived from Scutellaria , enhanced the NPs’ antibacterial efficacy by disrupting bacterial membranes and facilitating Zn 2+ influx, leading to cell wall rupture and metabolic disruption. In addition, Zn-BE NPs exhibited excellent photothermal conversion efficiency, enabling effective bactericidal action under near-infrared irradiation. This triple synergistic mechanism not only overcame the limitations of conventional Zn-based therapies but also sustained long-term antibacterial activity by preventing rapid bacterial metabolism. Our findings demonstrated that Zn-BE NPs could achieve complete bacterial eradication, showcasing expected potential in addressing antibacterial resistance. This research laid a foundation for the development of safer and more effective antibacterial agents, with implications for future applications in combating resistant infections.