Visualized DNA Aptamer-Functionalized Silver Nanoclusters against Tuberculosis

Tuberculosis (TB), a respiratory infectious disease caused by Mycobacterium tuberculosis (M.tb), poses a serious threat to human health due to its complex pathogenesis and limited treatment options. Diagnosing TB is challenging due to the poor sensitivity and specificity of current methods, while drug-resistance mechanisms further diminish the effectiveness of treatment. In this study, we developed a fluorescent nanoprobe named BM2-AgNCs by functionalizing silver nanoclusters with the DNA aptamer BM2. BM2-AgNCs facilitate efficient detection of lipoarabinomannan (LAM) and exhibit effective anti-M.tb activity, reducing bacterial viability by 80% both intracellularly and extracellularly. BM2 enhances the biocompatibility and targeting capabilities of AgNCs, which retain their fluorescence properties and antibacterial activity. AgNCs can serve as efficient quenchers of the FAM-labeled BM2, with fluorescence recovering in the presence of targets. Leveraging this property, we constructed a biosensor for the highly sensitive detection of LAM and for fluorescent tracking of M.tb. Regarding treatment, we demonstrated that BM2-AgNCs significantly inhibited M.tb activity while inducing M1 polarization in macrophages, resulting in a synergistic therapeutic effect. Furthermore, BM2-AgNCs can counteract immune evasion of M.tb by promoting phagolysosomal maturation. This work presents an integrated approach for TB diagnosis and treatment based on the fluorescent nanoprobe, utilizing the diverse fluorescent properties of the nanoprobe to visualize the underlying mechanisms.