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.