Monitoring Neuroinflammation with an HOCl-Activatable and Blood–Brain Barrier Permeable Upconversion Nanoprobe

A reliable tool for real-time tracking the neuroinflammatory progress is highly desired for interpretation and treatment of neurological disorders. Herein, a blood–brain barrier (BBB) permeable and HOCl-activatable upconversion (UC) nanoprobe with NIR emission was designed for visual study on neuroinflammation (NI) in vivo. This UC probe consists of three parts: upconversion nanoparticles (UCNPs) as signal reporter, the Cy-HOCl dye acting as energy acceptor of UCNPs as well as the recognition unit of HOCl, and amphiphilic polymers endowing the probe with biocompatibility and BBB permeability. Upon intravenous injection into mice, the probe crossed the BBB via low-density lipoprotein receptor related protein (LRP) mediated transcytosis and was then lightened up by overproduced HOCl in an NI process. This probe was able to differentiate inflammation and the normal state of the brain in LPS-induced NI and monitor the progress of NI occurring in mice with cerebral stroke, providing a practical tool for noninvasive and visual assessment of NI.