A Bioinspired Virus-Like Mechano-Bactericidal Nanomotor for Ocular Multidrug-Resistant Bacterial Infection Treatment.

Multidrug-resistant (MDR) bacteria and their associated biofilms are major causative factors in eye infections, often resulting in blindness and presenting considerable global health challenges. Presently, mechano-bactericidal systems, which combine distinct topological geometries with mechanical forces to physically induce bacterial apoptosis, show promising potential. However, the physical interaction process between current mechano-bactericidal systems and bacteria is generally based on passive diffusion or Brownian motion and lacks the force required for biofilm penetration; thus, featuring low antibacterial efficacy. Here, a biomimetic mechano-bactericidal nanomotor (VMSNT) is synthesized by functionalizing COOH-PEG-phenylboronic acid (PBA) on virus-like mesoporous silica, with subsequent partial coating of Au caps. Enhanced by self-thermophoresis capabilities and virus-like topological shapes, VMSNT significantly improves mechanical antibacterial effects and biofilm penetration. In addition, scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM) analyses demonstrate that VMSNT can precisely target bacteria within the infection microenvironment, facilitated by PBA's ability to recognize and bind to the peptidoglycan on bacterial surfaces. Remarkably, VMSNT is also effective in eliminating MDR bacteria and reducing inflammation in mice models of methicillin-resistant Staphylococcus aureus (MRSA)-infected keratitis and endophthalmitis, with minimal adverse effects. Overall, such a nanomotor presents a promising approach for addressing the challenges of ocular MDR bacterial infections.