A novel nanosensor for in situ detection of EV-miR-107 enables noninvasive tuberculosis diagnosis and treatment monitoring

Tuberculosis (TB) remains a leading cause of infectious death globally, creating an urgent need for rapid and non-invasive diagnostics. Extracellular vesicles (EVs) have emerged as promising carriers of disease-specific microRNAs with biomarker potential. This study identifies EV-miR-107 as a candidate host-response biomarker for TB, showing significant upregulation in TB patient plasma and a murine BCG infection model. To utilize this finding, an in-situ detection platform named CLiAN (CHA@Lipo@Aptamer Nanosensor) is developed. It utilizes cationic liposomes functionalized with CD63-specific aptamers and encapsulating catalytic hairpin assembly (CHA) probes to enable targeted EV fusion, facilitating efficient EV miRNA profiling within two hours. Clinically, CLiAN detects EV-miR-107 with 95.2% sensitivity (AUC = 0.87), outperforming sputum culture (36.4%) and Xpert MTB/RIF (54.5%). It also reliably monitors treatment response via dynamic changes in plasma EV-miR-107 levels (p = 0.001), correlating with clinical outcomes. This work establishes an integrated framework for TB management-from biomarker discovery to diagnostics and treatment monitoring-paving the way for improved point-of-care TB control.