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 Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) 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 in vitro and accelerate bone repair in vivo. 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.