Lysosome-Targeting Aggregation-Induced Emission Nanoparticle Enables Adoptive Macrophage Transfer-Based Precise Therapy of Bacterial Infections

Traditional antibacterial procedures are getting inefficientdueto the emergence of antimicrobial resistance, which makes alternativetreatments in urgent demand. However, the selectivity toward infectiousbacteria is still challenging. Herein, by taking advantage of theself-directed capture of infectious bacteria by macrophages, we developeda strategy to realize precise in vivo antibacterialphotodynamic therapy (APDT) through adoptive photosensitizer-loadedmacrophage transfer. TTD with strong reactive oxygen species (ROS)production and bright fluorescence was first synthesized and was subsequentlyformulated into TTD nanoparticles for lysosome targeting. TTD-loadedmacrophages (TLMs) were constructed by direct incubation of TTD nanoparticleswith macrophages, in which the TTD was localized in the lysosomesto meet the captured bacteria in the phagolysosomes. The TLMs couldprecisely capture and eradicate bacteria while being activated towardthe proinflammatory and antibacterial M1 phenotype upon light illumination.More importantly, after subcutaneous injection, TLMs could effectivelyinhibit bacteria in the infected tissue through APDT, leading to goodtissue recovery from severe bacterial infection. Overall, the engineeredcell-based therapeutic approach shows great potential in the treatmentof severe bacterial infectious diseases.