Microenvironment-responsive nanosystems for ischemic stroke therapy

Ischemic stroke, a common neurological disorder caused by impaired blood supply to the brain, presents a therapeutic challenge. Conventional treatments like thrombolysis and neuroprotection drugs lack ideal drug delivery systems, limiting their effectiveness. Selectively delivering therapies to the ischemic cerebral tissue holds great potential for preventing and/or treating ischemia-related pathological symptoms. The unique pathological microenvironment of the brain after ischemic stroke, characterized by hypoxia, acidity, and inflammation, offers new possibilities for targeted drug delivery. Pathological microenvironment-responsive nanosystems, extensively investigated in tumors with hypoxia-responsive systems as an example, could also respond to the ischemic cerebral microenvironment and achieve brain-targeted drug delivery and release. These emerging nanosystems are gaining traction for ischemic stroke treatment. In this review, we expound on the cerebral pathological microenvironment and clinical treatment strategies of ischemic stroke, highlight various stimulus-responsive materials employed in constructing ischemic stroke microenvironment-responsive nano delivery systems, and discuss the application of these microenvironment-responsive nanosystems in microenvironment regulation for ischemic stroke treatment.