Promising Roles of Selenium Nanoparticles in Anti-Tuberculosis Therapy: Opportunities and Challenges.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the most threatening infectious disease worldwide. Selenium, an essential micronutrient, is incorporated into selenoproteins such as glutathione peroxidase, which modulate lipid peroxidation and immune responses, thus playing pivotal roles in host defense against infection and control of Mtb dissemination. As an emerging class of selenium-based medicines, selenium nanoparticles (SeNPs) have demonstrated attractive anti-tuberculosis potential based on their favorable bioactivity, lower toxicity compared, high drug-loading capacity, sustained-release kinetics, and enhanced targeting specificity. Beyond their anti-TB potential, SeNPs have shown significant promise in various biomedical applications, including the treatment of diabetes, liver disease, Alzheimer's disease, and cancer, owing to their ability to modulate oxidative stress, inflammation, and apoptotic pathways. This review explores the relationship between selenium and the occurrence and development of tuberculosis, evaluates the potential of serum selenium as an auxiliary diagnostic biomarker, and outlines common preparation methods for SeNPs, including physical, chemical, and biological synthesis approaches. Furthermore, this review systematically summarizes the anti-tuberculosis functions of SeNPs, detailing multiple mechanisms such as accelerating Mtb-lysosome fusion, modulating intracellular ROS levels, driving M1 macrophage polarization, and inhibiting the PI3K/AKT/mTOR signaling pathway to collectively trigger autophagy and apoptosis in Mtb-infected macrophages. These insights may support the development of new anti-tuberculosis technologies based on SeNPs. Furthermore, we also address the key challenges hindering the clinical translation of SeNPs: the long-term in vivo tissue accumulation patterns of SeNPs have not been fully elucidated, long-term systemic nanotoxicity data remain scarce, almost all anti-tuberculosis studies are restricted to in vitro cell experiments and animal models, and the translational pathway from laboratory studies to clinical practice remains ambiguous.