Platelet Membrane-Based Nanoparticles for Targeted Delivery of Deferoxamine to Alleviate Brain Injury Induced by Ischemic Stroke

Background: Timely thrombolysis serves as the primary therapeutic approach for ischemic stroke, one of the most serious global public health problems, although reperfusion can cause severe ischemia reperfusion (I/R) injury. Oxidative stress and activation of cell death pathways are the main mechanisms of I/R injury. Our previous studies have demonstrated that iron overload stimulates the generation of reactive oxygen species and facilitates the activation of iron-dependent ferroptosis in the pathogenesis of I/R injury. Removal of excess free iron by deferoxamine (DFO), an iron chelator, may inhibit iron toxicity and reverse I/R-induced neurological deficits. Despite its therapeutic potential, DFO's clinical translation for I/R injury is hampered by rapid systemic clearance, suboptimal bioavailability, and a lack of ischemic lesion-targeting ability. Nanoscale delivery platforms enabling targeted DFO release in stroke lesions may overcome these pharmacokinetic barriers and enhance clinical outcomes. Methods: On the basis of the properties of liposomes in carrying hydrophilic substances and crossing the leaky blood-brain barrier in cerebral I/R, we first encapsulated DFO within traditional liposomes to improve its biocompatibility. Subsequently, inspired by the natural homing properties of platelets to damaged blood vessels during I/R injury, the isolated platelet membranes were coated onto the DFO-liposomes, thus endowing the nanodrug with the ability to target stroke lesion. Results: Our results demonstrate that Platesome-DFO exhibits accurate lesion-targeting ability and significantly decreases lesion iron content, thereby preventing neuronal ferroptosis and ultimately reversing neurological deficits in I/R mice. Conclusion: Platesome-DFO provides a novel therapeutic approach for cerebral I/R injury by regulating brain iron status and iron-dependent pathways, highlighting its promising application in the clinical treatment of cerebral I/R injury.