Dual-Channel NIR-II Probe for Simultaneous Tracking of Nitric Oxide and Methylglyoxal in Inflammation: Enabling Rapid Drug Efficacy Assessment

Nitric oxide (NO) and methylglyoxal (MGO) play a vital part in maintaining redox homeostasis, modulating substances, and signal transduction. Fluctuations in these signaling molecules are closely associated with various pathological processes. However, due to the absence of appropriate multifunctional fluorescent sensors, concurrent identification of NO and MGO has not been achieved in inflammatory diseases. Herein, a dual-responsive near-infrared window II fluorescent probe (TPA-4T) was rationally developed to monitor NO and MGO through its distinct emission channels concurrently. Upon NO exposure, TPA-4T formed the compound TPA-4T-NO with activated fluorescence signals at 980 nm, while MGO oxidation generated TPA-4T-MGO emitting at 1065 nm. This unique dual-responsive imaging property enabled TPA-4T to concurrently monitor the elevated NO and MGO levels in subcutaneous tumors through in vivo imaging for the first time, and the dual-channel visualization in the type 2 diabetes mellitus disease model was achieved. Most importantly, TPA-4T has successfully achieved utility in drug-induced liver injury, enabling not only diagnostic visualization but also rapid drug assessment in vivo. Undoubtedly, compared with single-analyte detection, the dual-biomarker strategy may provide enhanced sensitivity and reliability for inflammation-related disease diagnosis and the screening of therapeutic agents.