Membrane disruption and biomolecular enrichment-enhanced antibacterial therapy using peroxisome-inspired virus-like nickel nanoparticles

Efficient peroxidase mimetics-assisted therapeutic strategies have been developed to combat antibiotic-resistant pathogens with the overuse of antibiotics. Although promising, their antibacterial outcomes and clinical translation have been restricted by the bacterial targeting specificity, as well as the limited lifetime and diffusion distance of reactive oxygen species (ROS). Meanwhile, bacterial debris and their hazardous derivatives after antibacterial treatment can stimulate macrophages to produce pro-inflammatory factors and exacerbate inflammatory response. Herein, we develop a novel membrane disruption and biomolecular enrichment-enhanced antibacterial strategy with the assistance of smart peroxisome-inspired virus-like spiky nickel nanoparticles (SNNPs). The well-defined spiky surface of SNNPs endow them with the ability to capture bacteria and penetrate bacterial membranes, followed by the in situ catalytic generation of ROS to kill bacteria. Moreover, these SNNPs can efficiently remove bacterial debris after antibacterial treatment. Using an oral mucosal infection model, our well-developed system can kill bacteria and decrease the inflammatory response because of its Fenton-like catalytic activity, bacterial capture capability, and removal function of inflammatory-related mediators. Together, the design and presentation of our current system with synergistic functions of membrane disruption and biomolecular enrichment pioneer a promising biomimetic approach for oral infectious diseases, advancing the use of nano-sized catalysts in medicine.