Targeted Delivery of Dimethyl Malonate via a ZIF-8-Based Nanocarrier for Ischemic Stroke Treatment

To combat microglia-induced neuroinflammation after ischemic stroke, this study developed an intelligent nanodrug delivery system named DZIF@HA. The platform employs a ZIF-8 carrier to load the metabolic drug dimethyl malonate (DM), which is further functionalized with the AIRA peptide and hyaluronic acid for targeted delivery to inflamed microglial cells in the brain. Leveraging its pH-responsive properties, DZIF@HA achieves controlled drug release at the acidic lesion site, facilitating the shift of microglia from the pro-inflammatory M1 to the neuroprotective M2 phenotype. Experimental results demonstrate that this strategy successfully alleviates neuroinflammation, reduces infarct size, and promotes the recovery of neurological function, with a high safety profile, offering avenue for stroke treatment.