Tuberculosis is the second most fatal infectious disease; each year, it causes millions of deaths worldwide. Although several anti-TB drugs are currently available, the problem with these drugs is that they require a prolonged duration of treatment, with high drug doses. In addition, patient non-adherence to therapy subsequently leads to the development of multidrug-resistant and ex-tensively drug-resistant tuberculosis. Therefore, we need to develop an effective and robust nano-carrier-based drug delivery system to overcome these issues and improve the therapeutic potential of drug dose/duration and patient compliance. This review article focuses on the cur-rently available various nanotechnology-based therapeutic approaches, including lipid nanopar-ticles, polymeric particles, carbon nanotubes, glucan, and alginate-based nano-carrier systems for effective anti-TB drug delivery to host macrophage for mycobacterium killing. Finally, we also present some promising recent nanotechnology-based mycobacterial detection systems us-ing silver nanoparticles, silica nanoparticles, magnetic nanoparticles, quantum dots, and magnet-ic barcode assay that have recently emerged as the latest diagnostic tool. Functionalized nano-materials for emerging Aggregation-induced photodynamic therapy as next-generation theranostics have also been discussed as a novel option for TB diagnosis and therapy.

Tuberculosis (TB), attributable to Mycobacterium tuberculosis (M.tb), constitutes a formidable global health challenge, particularly with the proliferation of multidrug-resistant (MDR) strains. The efficacious clearance of M.tb from host cells is imperative for mitigating infection and averting disease progression. Autophagy, an intricate cellular mechanism for degrading and recycling biomolecules, plays a pivotal role in the immune response to M.tb by facilitating the degradation of intracellular pathogens through the formation of autophagosomes and their subsequent fusion with lysosomes. This study elucidates the therapeutic efficacy of DYDGP microparticles in M.tb-infected macrophages. DCFHDA staining elucidated that DYDGP significantly enhances macrophage membrane integrity and amplifies reactive oxygen species (ROS) production compared to YDGP, even in the presence of NOX-2 inhibitors. Furthermore, DYDGP promotes the biogenesis of acidic vesicular organelles and phago-lysosomal maturation, as corroborated by acridine orange and Lysotracker Red staining. Immunofluorescence and dansylcadaverine staining evidenced that DYDGP enhances autophagy induction and LC3 puncta formation in infected macrophages at both 30 min and 24 h. Protein expression analyses demonstrated elevated levels of NOX-2 and LC3, confirming autophagy induction. Antimycobacterial efficacy assessments revealed that DYDGP treatment engendered significant reductions in colony-forming units (CFUs) for H37Rv (64, 40, 19), MDR32420 (44, 35, 18), MDR32422 (44, 39, 21), and MDR32521 (38, 22, 18) at 30 min, 24 h, and 48 h, respectively. These findings accentuate DYDGP's potential to substantially attenuate M.tb burden, including in MDR strains, thereby positioning it as a promising adjunctive therapy for augmenting tuberculosis treatment.