Inhalable Ce Nanozyme-Backpacked Phage Aims at Ischemic Cerebral Injury by M1-Microglia Hitchhiking

There is a desperate need for precise nanomedications to treat ischemic cerebral injury. Yet, the drawbacks of poor delivery efficiency and off-target toxicity in pathologic parenchyma for traditional antioxidants against ischemic stroke result in inadequate brain accumulation. M13 bacteriophages are highly phagocytosed by M1-polarized microglia and can be carried toward the neuroinflammatory sites. Here, a bio-active, inhalable, Ce_0.9Zr_0.1O₂-backpacked-M13 phage (abbreviated as CZM) is developed and demonstrates how M13 bacteriophages are taken up by different phenotypes’ microglia. With the M1 microglia's proliferating and migrating, CZM can be extensively and specifically delivered to the site of the ischemic core and penumbra, where the surviving nerve cells need to be shielded from secondary oxidative stress and inflammatory cascade initiated by reactive oxygen species (ROS). With non-invasive administration, CZM effectively alleviates oxidative damage and apoptosis of neurons by eliminating ROS generated by hyperactive M1-polarized microglia. Here, a secure and effective strategy for the targeted therapy of neuroinflammatory maladies is offered by this research.