Phagocyte-inspired supramolecular self-assembly design of abiotic cell-mimics for pathogen recognition and eradication.

Abstract

Pathogens are rapidly evolving resistance against both antibiotics and the human immune system. Artificial cells provide an attractive strategy to engineer cell-like systems from simple abiotic materials, offering tunable properties and facile synthesis compared to complex biological components. Inspired by natural phagocytes, we have developed a phagocyte-inspired supramolecular antimicrobial macrostructure based on self-assembly via dative bonds. We developed a phagocyte-inspired supramolecular antimicrobial macrostructure that emulates three phagocytic functions abiologically: (i) rapid pathogen capture, achieving ∼70% binding within 30min, being faster than raw phagocytes, (ii) bacterial eradication via vanadyl-driven ROS generation, and (iii) self-limiting apoptosis-like deactivation upon pathogen interaction. SEM and ICP-MS confirm concentration-dependent dismantling, with ∼100% Co and V release at pathogen-appropriate proportional concentrations (4-20 μg/mL), corroborated by DFT analysis showing Co recognition of bacterial amines. The material eradicates >90% of biofilms in vitro, outperforms levofloxacin and metronidazole by ∼2×, and effectively treats biofilm-associated wound infections and bacterial keratitis in vivo. We describe this material as a phagocyte-inspired supramolecular cell-mimic, a rationally designed abiotic assembly that emulates three key steps of phagocytosis. Comprehensive characterization and combined experimental and theoretical analysis elucidate the chemical and molecular processes underlying its phagocyte like antibacterial cascade. Bacterial metabolomic and genomic profiling together with multimodal analysis provide insights into dative bond driven assembly self-deactivation and antibacterial activity. This study establishes a blueprint for the development of next-generation abiotic artificial cell-mimics and smart antimicrobial materials. STATEMENT OF SIGNIFICANCE: Phagocyte-inspired CoVO_x-SIOC abiotic cell-mimics achieve rapid pathogen capture and ROS-mediated eradication. Supramolecular design enables a self-limiting "apoptosis-like" deactivation to prevent collateral damage. The material eliminates >90% of biofilms, significantly outperforming conventional antibiotics in vitro. In vitro and in vivo models and analysis demonstrate effective treatment of biofilm-associated wound infections and bacterial keratitis and underlying mechanisms.