Significance
Ischemic stroke is recognized as a leading cause of death and disability in the world. Rational design of nanomedicine to accelerate thrombolysis and sequentially avoid thrombolysis-mediated reperfusion injury is still a challenge. Herein, a biomimetic nanovesicle (tMP) was developed for sequential ischemic stroke treatment. It could overcome the drawbacks of free tPA for safe thrombolysis: i) platelet membrane biomimetic coating significantly increases thrombus targeting; ii) NIR-mediated photothermal of natural melanin precise controlled release of tPA in thrombus in situ, and local hyperthermia also increases the thrombolytic activity of tPA. Notably, released melanin nanoparticles (4.5 nm) accompanied by hemoperfusion can across BBB and avoid ischemia-reperfusion injury through free radical scavenging and inflammation/immune response suppression.
Statement of significance
Ischemic stroke is recognized as a leading cause of death and disability in the world. Rational design of nanomedicine to accelerate thrombolysis and sequentially avoid thrombolysis-mediated reperfusion injury is still a challenge. Herein, a biomimetic nanovesicle (tMP) was developed for sequential ischemic stroke treatment. It could overcome the drawbacks of free tPA for safe thrombolysis: i) platelet membrane biomimetic coating significantly increases thrombus targeting; ii) NIR-mediated photothermal of natural melanin precise controlled release of tPA in thrombus in situ, and local hyperthermia also increases the thrombolytic activity of tPA. Notably, released melanin nanoparticles (4.5 nm) accompanied by hemoperfusion can across BBB and avoid ischemia-reperfusion injury through free radical scavenging and inflammation/immune response suppression.