NIR-II aggregation-induced emission nanoparticles camouflaged with preactivated macrophage membranes for phototheranostics of pulmonary tuberculosis.

Phototheranostics, which allows simultaneous diagnosis and therapy, offers notable advantages in terms of noninvasiveness, controllability and negligible drug resistance, presenting a promising approach for disease treatment. By integrating second near-infrared (NIR-II, 1,000-1,700 nm) phototheranostic agents characterized by aggregation-induced emission (AIE) and cell membranes with specific targeting capacity, we have developed a versatile type of biomimetic nanoparticle (NP) for precise phototheranostics of pulmonary tuberculosis (TB). Coating the phototheranostic agents with preactivated macrophage membranes results in the formation of biomimetic NPs, which exhibit specific binding to TB through a lesion-pathogen dual-targeting strategy, allowing the accurate detection of Mycobacterium tuberculosis via NIR-II fluorescence imaging and precise photothermal therapy using the irradiation of a 1,064 nm laser. In comparison with traditional treatments, small individual granulomas (0.2 mm in diameter) in TB-infected mice are visualized, and improved antibacterial effects are achieved upon NP administration. Here we present a standardized workflow for the synthesis of the NIR-II AIE agents, their use for the fabrication of the biomimetic NPs and their in vitro and in vivo applications as phototheranostics against M. tuberculosis. The preparation and characterization of the NIR-II AIE agents requires ~8 d, the synthesis and characterization of the phototheranostic NPs requires ~8 d, the validation of in vitro targeting capacity and photothermal eradication requires ~26 d, and the in vivo NIR-II fluorescence imaging and imaging-guided photothermal therapy requires ~74 d. All procedures are straightforward and suitable for clinicians or researchers with prior training in organic synthesis and biomedical engineering.