Nanotheranostic Trojan Horse for Visualization and Photo-Immunotherapy of Multidrug-Resistant Bacterial Infection

Abstract

Abstract Effective diagnosis and therapy for bacterial infections, especially those caused by multidrug-resistant (MDR) species, greatly challenge current antimicrobial stewardship. Monocytes, which can chemotactically migrate from the blood to infection site and elicit a robust infection infiltration, provides a golden opportunity for bacterial theranostics. Here, an endogenous cell hitchhiking nano-Trojan Horse was facilely engineered using mannose-functionalized manganese-eumelanin coordination nanoparticles (denoted as MP-MENP) for precise two-step localization and potent photothermal-immunotherapy of complicated MDR bacterial infection. Taking advantage of the selective recognition between mannose and inflammation-associated monocytes, the MP-MENP could be passively piggybacked to infection site by circulating monocytes, and also actively target infiltrated monocytes that are already accumulated in infection microenvironment. Such dual-pronged targeting enabled an efficient photoacoustic and magnetic resonance imaging of bacterial infection. Upon laser irradiation, the MP-MENP robustly produced local hyperemia to ablate pathogenic bacteria, both extracellularly and intracellularly. Further combined with the synergistic effect of immunogenic cell death induced by photothermal therapy and macrophage reprogramming by MP-MENP, the immunosuppressive infection microenvironment was significantly relieved, allowing an enhanced antibacterial immunity. Collectively, the proposed nanotheranostic Trojan Horse, which integrate dual-pronged targeting, precise imaging diagnosis, and high-performance photothermal immunotherapy, promise a new way for complete eradication of MDR bacterial infection.