Photoacoustic imaging-guided, synchronously targeted thrombolysis and neuroprotection of acute ischemic stroke.

Acute ischemic stroke (AIS) is a major cause of disability and mortality worldwide, typically resulting from a thrombus that blocks cerebral blood flow. Current treatments focus on thrombolysis and neuroprotection, with recombinant tissue plasminogen activator (rt-PA) and edaravone (Eda) as key drugs. However, their therapeutic efficacy is constrained by poor targeting, leading to suboptimal drug delivery to the brain. Herein, we develop a biomimetic delivery system (PLEA, platelet membrane-liposome hybrid delivery system encapsulating Eda and rt-PA) by hybridizing platelet membranes with liposomes, leveraging natural thrombus-targeting ability of the platelet membrane to enhance drug delivery efficiency. PLEA effectively targeted thrombus sites, synchronously enhancing thrombolysis and providing neuroprotection in a mouse model of AIS. Photoacoustic (PA) imaging was used to monitor clot formation and assess changes in intracranial blood flow and oxygen levels. These findings indicate that PA imaging-guided PLEA treatment represents a promising approach for precise stroke treatment.