NIR‐II AIE Luminogen‐Based Erythrocyte‐Like Nanoparticles with Granuloma‐Targeting and Self‐Oxygenation Characteristics for Combined Phototherapy of Tuberculosis

Abstract

Tuberculosis, a fatal infectious disease caused by Mycobacterium tuberculosis (M.tb), is difficult to treat with antibiotics due to drug resistance and short drug half-life. Phototherapy represents a promising alternative to antibiotics in combating M.tb. Exploring an intelligent material allowing effective tuberculosis treatment is definitely appealing, yet a significantly challenging task. Herein, an all-in-one biomimetic therapeutic nanoparticle featured by aggregation-induced second near-infrared emission, granuloma-targeting, and self-oxygenation is constructed, which can serve for prominent fluorescence imaging-navigated combined phototherapy toward tuberculosis. After camouflaging the biomimetic erythrocyte membrane, the nanoparticles show significantly prolonged blood circulation and increased selective accumulation in tuberculosis granuloma. Upon laser irradiation, the loading photosensitizer of aggregation-induced emission photosensitizer elevates the production of reactive oxygen species (ROS), causing M.tb damage and death. The delivery of oxygen to relieve the hypoxic granuloma microenvironment supports ROS generation during photodynamic therapy. Meanwhile, the photothermal agent, Prussian blue nanoparticles, plays the role of good photothermal killing effect on M.tb. Moreover, the growth and proliferation of granuloma and M.tb colonies are effectively inhibited in the nanoparticle-treated tuberculous granuloma model mice, suggesting the combined therapeutic effects of enhancing photodynamic therapy and photothermal therapy.