Lysosome-Targeted Si-rhodamine Derivative for NO Imaging in Mice Brain with Neurological Diseases

Nitric oxide (NO) is an intracellular and intercellular messenger, regulating cellular functions in different manners. Intracellular vesicular acidic compartments, such as lysosomes, are essential digestive organelles of the cells, where the abnormal changes of NO concentration can alter the microenvironmental change and are related with the progression of various diseases, for instance, neuroinflammation and Wadatson's disease. Herein, we presented <b>dL-SiR-NO</b> as an effective lysosome-targeted NIR fluorescent probe for the sensing, which was applied in detecting <i>in situ</i> NO level changes in the brain with neuroinflammation. The probe is designed by incorporating the lysosome-targeting unit-morpholine to the deoxy spiro-lactam-silyl rhodamine fluorophore, which is further conjugated with <i>o</i>-diaminobenzene as the NO recognition moiety. <b>dL-SiR-NO</b> showed a higher sensitivity to NO in an acidic microenvironment, along with a good sensing selectivity. Furthermore, using this near-infrared fluorescent probe, we imaged the changes of NO level in living cells and uncovered a significant increase of NO concentration in mouse brains with neuroinflammatory diseases. This sensing probe could provide new opportunities to evaluate NO-related inflammatory diseases progression, therapeutic monitoring, and anti-inflammatory drug screening.