Wide-Spectrum Nano-Antibiotics Based on TPA-Py@AuNCs⊂BSA for Multimodal Synergistic Therapy of Drug-Resistant Bacteria and Wound Infections

To meet the high requirements of biomedical applications in antimicrobial agents, it is crucial to explore efficient nano-antimicrobial agents with no resistance and good biocompatibility for treating infected wounds. In this study, composite nano-antibiotic TPA-Py@AuNCs⊂BSA nanoparticles (TAB NPs) are prepared using hollow mesoporous Au nanocages (AuNCs) loaded with a photosensitizer (namely TPA-Py) with D-π-A structure showing aggregation-induced emission properties. When TPA-Py is encapsulated in the cavity of AuNCs, its fluorescence is suppressed. In the presence of photothermal induction, TPA-Py can be released from the AuNCs, allowing for the restoration of fluorescence illumination and the specific imaging of Gram-positive bacteria. TAB NPs demonstrate outstanding antimicrobial activity against a variety of bacteria, and this multimodal antimicrobial property does not lead to the development of bacterial resistance. In vitro experiments show that TAB NPs could eliminate bacteria and ablate bacterial biofilm. In vivo experiments show that the synergistic antimicrobial effect of TAB NPs has a significant positive impact on the treatment of infected wounds, including rapid antibacterial action, promotion of M2 macrophage polarization, and enhancement of chronic wound healing. This study provides an effective strategy for developing wide-spectrum nano-antibiotics for the ablation of bacterial biofilms and the treatment of infected wounds.