A novel acridine-based mitochondria-targeted near-infrared fluorescent probe for the detection of HOCl/ONOO- in vivo

Fluorescence imaging plays a key role in disease diagnosis. Fluorescent probes constructed with near-infrared (NIR) dyes exhibit negligible light damage to the organism, and excellent deep-tissue penetration. The higher intracellular concentrations of HOCl/ONOO^- in cancer cells versus normal cells make these species valuable biomarkers for disease diagnosis. Thus, a novel NIR fluorescent probe AcA-MO is proposed for HOCl/ONOO^- detection. AcA-MO is constructed based on a new acridine dye with morpholine groups modifying both ends. AcA-MO has the advantages of rapid response (within 5 s), visual color transition (from colorless to lake green), high sensitivity (detection limits of 10.9 nM for HOCl and 17.5 nM for ONOO^-), and excellent selectivity. Furthermore, AcA-MO demonstrated accurate mitochondrial targeting capability. The capabilities of AcA-MO extended from HOCl/ONOO^- monitoring in cells and zebrafish to successful implementation of in vivo imaging. Notably, the reaction of AcA-MO with HOCl/ONOO^- resulted in a novel NIR dye Ac-MO with excellent properties such as good water solubility, high molar absorbance coefficient (7.82 × 10⁴ L·mol^-1·cm^-1) and fluorescence quantum yield (Φ = 0.08). Ac-MO provides an innovative design platform for the construction of NIR fluorescent probes. It is anticipated to facilitate the design of additional ROS fluorescent probes, offering robust tools for clinical diagnosis.