Rational design of an activatable probe for sensing peroxynitrite in diabetic wound

To address the impaired healing of diabetic wounds driven by the overproduction of peroxynitrite (ONOO − ), we developed HD-ONOO , a near-infrared (NIR) activatable fluorescent probe based on a hemicyanine scaffold. The probe utilizes an ONOO − -triggered degradation of a boronic acid pinacol ester moiety to initiate an intramolecular charge transfer (ICT) process, resulting in a robust fluorescence “turn-on” response at 750 nm. HD-ONOO exhibits exceptional selectivity and high sensitivity, with a calculated limit of detection (LOD) of 0.02 μM. Beyond monitoring endogenous ONOO − fluctuations in RAW264.7 cells, the probe enabled high-contrast visualization and spatiotemporal quantification of ONOO − concentration in both the serum and cutaneous wound beds of diabetic mice. Furthermore, the probe successfully tracked the attenuation of ONOO − levels following metformin (MET) administration, highlighting its utility for evaluating therapeutic efficacy. Collectively, this research establishes HD-ONOO as a versatile molecular imaging tool for the early diagnosis, precision monitoring, and therapeutic assessment of diabetes-associated inflammatory complications.