Visualizing Oxidative Stress Level for Timely Assessment of Ischemic Stroke via a Ratiometric Near-Infrared-II Luminescent Nanoprobe.

Abstract

Ischemic stroke (IS) characterized with high morbidity and mortality rates is considered as one of the most dangerous brain diseases. The timely assessment of IS is crucial for making a clinical decision due to the severity of IS featured with time-dependence. Herein, we develop a highly reactive oxygen species (HROS)-responsive ratiometric near-infrared-II (NIR-II) nanoprobe based on a dye-sensitized system between IR-783 dye and lanthanide-doped nanoparticles. Once intravenously injected into the mice, the probe is rapidly accumulated at a lesion site by recognizing the activated endothelial cell or impaired blood-brain barrier (BBB) in the ischemic area and further responds to HROS, thereby allowing in vivo imaging of the oxidative stress level. The probe is not only able to discriminate the salvageable ischemic tissue from infarcted stroke core by visualizing the enriched degree of the probe at the lesion site but also can grade the salvageable ischemic tissue by analyzing the oxidative stress level. In addition, the ischemia area was clearly delineated by NIR-II luminescence imaging after cerebral ischemia for 30 min, which is significantly earlier than with the magnetic resonance imaging (MRI) method, thereby providing a practical tool for the timely assessing of IS.