Albumin-seeking near-infrared-II probe evaluating blood–brain barrier disruption in stroke

Blood-brain barrier (BBB) disruption after stroke is closely associated with brain tissue edema and neuronal injury, which requires accurate assessment. However, there is a lack of appropriate BBB imaging modality in vivo. As albumin in the blood could cross the damaged BBB into brain tissue after stroke, it serves as a biomarker for BBB disruption. Therefore, we aimed to develop an albumin-seeking near-infrared (NIR) probe to assess BBB disruption in stroke. We proposed a chemoselective strategy for seeking albumin with NIR dyes and identified an optimal probe to evaluate BBB disruption in stroke. The probe combined a NIR fluorescent dye with inherent albumin-targeting moieties and exhibited high affinity and selectivity for binding to albumin. Using a mouse stroke model, the probe displayed a high-resolution visualization of the location and extent of BBB disruption in vivo and correlated well with BBB leakage measured by Evans blue ex vivo. A dual-channel NIR-II imaging was successfully used to simultaneously assess BBB disruption and cerebral perfusion after stroke. Furthermore, we applied this method to dynamically evaluate the BBB disruption process and reperfusion of thrombolytic therapy in a stroke model in real time, which showed excellent application value. We developed an albumin-seeking NIR probe that accurately evaluated BBB disruption in a safe, non-invasive and real-time manner in various stroke models, and has a great potential guiding stroke treatment in a real-time manner.