Mn₃o₄@nanoerythrocyte-T7 Peptide: A Biomimetic Nanoplatform for Targeted Ischemic Stroke Therapy

Ischemic stroke is a major cause of mortality and long-term neurological disability worldwide, primarily resulting from blockage of cerebral blood vessels and subsequent ischemia-reperfusion injury. Excessive production of reactive oxygen species (ROS), inflammation, neuronal apoptosis and blood-brain barrier (BBB) disruption significantly contribute to neurological damage following stroke. Conventional therapies mainly focus on restoring blood flow but provide limited protection against oxidative stress and reperfusion-associated injury. Therefore, the development of multifunctional neuroprotective nanomedicines has emerged as a promising therapeutic strategy. Nanosponges are porous, biocompatible nanoparticles capable of encapsulating both hydrophilic and lipophilic substances, offering advantages such as enhanced stability, targeted delivery and improved therapeutic efficacy. Among these, Mn3O4@nanoerythrocyte-T7peptide (MNET) represents an innovative biomimetic nano sponge system designed for targeted ischemic stroke therapy. This formulation consists of manganese oxide (Mn3O4) nanoparticles enclosed within nano erythrocyte membranes and functionalized with T7 peptide to enhance BBB penetration and brain targeting. The Mn3O4 nanoparticles exhibit potent ROS-scavenging nanoenzyme activity, thereby reducing oxidative damage in ischemic brain tissue. The nano erythrocyte membrane improves biocompatibility, prolongs circulation time and supports adaptive oxygen regulation during ischemia brain regions. Experimental studies have demonstrated that MNET significantly reduces infarct volume, decreases neuronal apoptosis and improves neurological recovery. Overall, Mn3O4@nanoerythrocyte-T7 offers a promising biomimetic nanotherapeutic approach for ischemic stroke management by simultaneously addressing oxidative stress, hypoxia and reperfusion injury, thereby presenting potential advantages over conventional stroke therapies.