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 and often leading to severe neurological impairment and irreversible brain damage. 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) by hybridizing platelet membranes with liposomes, leveraging natural thrombus-targeting ability of platelet membrane to enhance drug delivery efficiency. Eda was encapsulated in the lipid bilayer of PLEA, while rt-PA was loaded into the core. PLEA (platelet membrane-liposome hybrid delivery system encapsulating Eda and rt-PA) effectively targeted thrombus sites, enabling localized drug delivery, 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, highlighting its potential for evaluating therapeutic efficacy. These findings indicate that PA imaging-guided PLEA treatment represents a promising approach for precise stroke treatment. Overall design: RNA-seq profiling of infarct mouse cortex tissues at 3 days after saline or PLEA nanoparticle treatment.