Rationally designed lipid droplets-selective two-photon nitric oxide probe for high-fidelity neuroinflammation evaluation

Abstract Neuroinflammation is pervasive throughout various neurodegenerative diseases and is regarded as one of the main destructive effects of these diseases. A large quantity of nitric oxide (NO) will be produced by nitric oxide synthase (NOS) in inflammatory cells, and thus has been considered as a favorable index to reflect the level of inflammation. However, NO concentration in cells is commonly affected by neuronal nitric oxide synthase (nNOS), which makes conventional NO sensors unable to accurately evaluate the level of neuroinflammation with high fidelity. Fortunately, during a neuroinflammation process, the significantly increased lipid droplets in brain cells can supply another indicator for evaluating neuroinflammation. Herein, a lipid droplet-targeted two-photon nitric oxide probe (SUN-TAN) was designed for monitoring NO in lipid droplets, thus assessing the level of neuroinflammation with high fidelity. Upon reacting with NO and being excited by near-infrared light at 780 nm, SUN-TAN exhibits an emission peak at 635 nm. The applications of SUN-TAN in NO determination and imaging in both BV-2 cells and brain tissues of mice suffering from neuroinflammation induced by ischemic brain injury have been achieved.