A Near-Infrared Fluorescent Probe for Monitoring of LACTB Activity in NSCLC Diagnosis and Therapy.

Abstract

This study introduces HD-LACTB (Hemicyanine Dye-LACTB), a novel near-infrared fluorescent probe designed for real-time imaging of β-lactamase (LACTB) activity in nonsmall cell lung cancer (NSCLC). HD-LACTB incorporates a semicyanine-based signal-reporting unit that undergoes structural activation upon interaction with LACTB, enabling sensitive fluorescence detection. Compared to previous probes, HD-LACTB exhibits superior deep-tissue penetration, high selectivity, and low cytotoxicity, making it well-suited for in vivo applications. The probe effectively targets the mitochondria and enables intracellular imaging of LACTB activity during tumor induction and drug treatment. In both subcutaneous and orthotopic lung cancer mouse models, HD-LACTB demonstrated consistent and robust performance, accurately visualizing LACTB-mediated metabolic alterations. These results highlight the clinical potential of HD-LACTB as a noninvasive tool for early diagnosis, tumor staging, therapeutic monitoring, and personalized treatment assessment in NSCLC.