An Ischemia-Homing Bioengineered Nano-Scavenger for Specifically Alleviating Multiple Pathogeneses in Ischemic Stroke

Background: Ischemic stroke is one of the most serious global public health problems. However, the performance of current therapeutic regimens is limited due to their poor target specificity, narrow therapeutic time window, and compromised therapeutic effect. To overcome these barriers, we designed an ischemia-homing bioengineered nano-scavenger by camouflaging a catalase (CAT)-loaded self-assembled tannic acid (TA) nanoparticle with a M2-type microglia membrane (TPC@M2 NPs) for ischemic stroke treatment. Results: : The TPC@M2 NPs can on-demand release TA molecules to chelate excessive Fe 2+ , while acid-responsively liberating CAT to synergistically scavenge multiple ROS (•OH, •O 2 - , and H 2 O 2 ). Besides, the M2 microglia membrane not only can be served as bioinspired therapeutic agents to repolarize M1 microglia into M2 phenotype but also endows the nano-scavenger with ischemia-homing and BBB-crossing capabilities. Conclusions: : The nano-scavenger for specific clearance of multiple pathogenic elements to alleviate inflammation and protect neurons holds great promise for combating ischemic stroke and other inflammation-related diseases.