Infection responsive bio-nanoparticles as "molecular sprayer " for infection-repair integration via direct sterilization and macrophage polarization regulation

Bone tissue destruction and related complications caused by bacterial infection remain a major challenge in clinical treatment. Existing therapies generally fail to balance the process of infection control and tissue repair simultaneously. In this study, infection microenvironmental-responsive multifunctional "molecular sprayer" nanocomposites (NP@D/AMP) were developed by loading 2-(1, 8-naphthidine -2-yl) phenol (2-NP) onto dendritic mesoporous silica nanoparticles (DMSNs), then encapsulating GW18 with polydopamine for sealing, which achieved the integrated functions of antibacteria, immune regulation and promoting bone formation. NP@D/AMP can sequentially release GW18 and 2-NP under the acidic microenvironment at the infectious site, where GW18 shows strong antibacterial and biofilm inhibition ability against <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and <i>Escherichia coli</i> (<i>E. coli</i>) through electrostatic interaction as well as 2-NP activates macrophages into M1 macrophages to synergistically enhance the antibacterial immune response and improve the inflammatory microenvironment. Notably, NP@D/AMP can also significantly promote osteogenic differentiation <i>in vitro</i> and accelerate bone repair <i>in vivo</i>. In brief, nanocomposite NP@D/AMP has demonstrated sustained and surprising antibacterial activity with macrophage regulation and bone formation efficacy in the treatment model of bone infection. Our study provides an innovative "antibacteria - immune balance - tissue repair" synergistic integrated therapy strategy for infectious bone defects.