Uptake of Biomimetic Nanovesicles by Granuloma for Photodynamic Therapy of Tuberculosis.

The antimicrobial resistance of Mycobacterium tuberculosis (M. tuberculosis) is a challenge in the antibiotic treatment of tuberculosis (TB). Herein, we aimed to examine a photodynamic therapy for TB that has a low risk of drug resistance and involves biomimetic macrophage membranes combined with a photosensitizer, chlorin e6 (Ce6; hereinafter, C-MV). We used Mycobacterium marinum (M. marinum), a waterborne pathogen closely related to M. tuberculosis, which causes TB-like infections in ectotherms but not in humans. The mouse tail granuloma model induced by M. marinum is a relatively mature TB model developed by our team. C-MV nanoparticles were prepared and injected intravenously, showing longevity in circulation due to the properties of the macrophage membrane, which protects them from being eliminated from the blood. They were then guided to tuberculous granulomas, helping deliver precise photodynamic therapy. Ce6 is a classical photosensitizer that triggers the production of reactive oxygen species under laser irradiation, causing M. marinum death. The C-MV nanoparticles showed good compatibility and a long circulation time, effectively inhibiting the proliferation and infiltration of M. marinum, providing a new paradigm for TB treatment.