Brain-targeted NIR-I/NIR-II ratiometric fluorescence nanoprobe for in situ monitoring of dynamic H2S fluctuations during epileptic seizures

Recurrent seizures associated with epilepsy are intricately linked to the redox homeostasis within the brain. Hydrogen sulfide (H₂S) functions as a critical intracellular antioxidant and can be recognized as an indicator of epileptic seizures. However, the absence of reliable tools poses significant challenges for precise in vivo monitoring of cerebral H₂S levels in deep tissues. Herein, we developed a ratiometric fluorescent nanoprobe CNPs@cRGD that emits dual-channel fluorescence (F₇₁₅ and F₁₀₄₅) within the first/second near-infrared (NIR-I/NIR-II) window, enabling accurate ratiometric fluorescence imaging of cerebral H₂S levels and facilitating the diagnosis of epilepsy. Specifically, CNPs@cRGD was obtained by loading a H₂S-specific NIR-I/NIR-II ratiometric reporter Cy-NO₂ with a cyclic arginyl-glycyl-aspartic acid (cRGD)-functionalized carrier DSPE-mPEG-cRGD. The cRGD modification significantly enhanced blood-brain barrier (BBB) penetration and intracranial accumulation of CNPs@cRGD, thereby facilitating sensitive fluorescence ratio (F₇₁₅/F₁₀₄₅) enhancement in response to pathologic H₂S levels within the brain. More importantly, by integrating the deep tissue penetration of NIR fluorescence, the high fidelity of ratiometric signals, and cRGD-driven brain targeting, CNPs@cRGD achieved accurate and quantitative visualization of fluctuations in cerebral H₂S during the onset and progression of epilepsy. This intelligent platform may serve as a powerful tool for the precise in situ monitoring of relevant brain diseases.