Self‐Templated ZnGly Nanoparticles With Dual Antibacterial and Immunomodulatory Functions for Accelerated Infected Wound Healing

ABSTRACT The wound healing process is often hindered by bacterial infection and excessive inflammation, impeding normal tissue repair and bringing a huge medical burden. Various treatment strategies, including antibiotics and wound dressings, have been developed to address these challenges. However, these approaches often suffer from limitations such as antibiotic resistance, insufficient immune regulation, and poor wound microenvironment modulation, leading to unsatisfactory therapeutic outcomes. Here, we designed and synthesized a kind of endocytosed zinc ion‐glycine (ZnGly) self‐templated nanoparticles (NPs) through a simple self‐template method, which exhibited excellent antibacterial and immunomodulatory properties. ZnGly NPs showed a pH‐responsive behavior, allowing for rapid release of bioactive components in the acidic environment of lysosomes. ZnGly NPs with good cytocompatibility effectively modulated macrophage polarization, enhancing the expression of anti‐inflammatory factors while inhibiting the expression of pro‐inflammatory factors. Interestingly, mechanistic studies revealed that ZnGly NPs alleviated LPS‐induced inflammatory responses by promoting Cl − influx, inhibiting Ca 2+ influx, and then regulating the NF‐κB signaling pathway. Furthermore, ZnGly NPs killed free bacteria and removed biofilm efficiently. The infected wound‐healing promotion of ZnGly NPs was validated in an infected mouse skin model, highlighting the therapeutic potential of antibiosis and immunoregulation. Overall, the pH‐responsive ZnGly NPs possess great potential in managing bacterial‐infected wound healing.