Biomimetic mycobacterial dual spatiotemporal targeting induces trained immunity for tuberculosis photothermal immunotherapy and relapse prevention
In this study, a biomimetic DNA tetrahedral phototherapy system (TDN+AIE@MM), modified with Mycobacterium marinum membrane, was constructed to mimic the trained immune patterns of primary and secondary immunity, enabling dual spatiotemporal targeting of tuberculous granulomas and draining lymph nodes. Leveraging molecular recognition mediated by naturally occurring ligands on the bacterial membrane, the system precisely delivered payloads to immunosuppressive granulomas and antigen-presentation-retarded lymph nodes. Upon near-infrared II (NIR-II) laser irradiation, the integrated AIE photothermal agent generated localized hyperthermia to directly eliminate intracellular Mycobacterium tuberculosis, while simultaneously releasing abundant pathogen-associated antigens to further activate adaptive immunity and long-term memory immune responses.