Activatable photoacoustic probe for noninvasive monitoring of hepatic nitric oxide in diabetes progression.

Nitric oxide (NO) plays crucial roles in physiological and pathological processes, yet existing probes for NO detection suffer from limitations in sensitivity, selectivity, and biocompatibility. This study developed a novel benzothiazole-based donor-acceptor-donor (DAD) organic nanoprobe for high-performance NO sensing. The designed small molecule probe exhibited near-infrared emission and NO-triggered cyclization that significantly enhanced intramolecular charge transfer, leading to distinct optical and photoacoustic signal changes. Encapsulation with mPEG-DSPE yielded water-dispersible nanoparticles with excellent stability in physiological media and minimal cytotoxicity. The nanoprobe demonstrated exceptional selectivity for NO over reactive species and biological thiols. In streptozotocin-induced diabetic mice, the nanoprobe successfully monitored hepatic NO levels through photoacoustic imaging, showing stage-dependent signal increases that correlated with diabetes mellitus (DM) progression markers including blood glucose, liver enzymes, and histopathological changes. This work provides both a valuable tool for studying NO biology and a design strategy for activatable molecular probes.