A CREKA-modified multifunctional nanoplatform for targeted thrombolysis: ain vitrocharacterization of efficacy and...

Retinal thrombotic diseases, a major cause of vision impairment, lack effective treatments that directly resolve vascular occlusion. To address this challenge, we developed a novel multifunctional nanoplatform for targeted thrombolysis: PLGA-PFP-rtPA nanoparticles modified with the fibrin-targeting peptide CREKA (PPrC NPs). The nanoparticles were successfully fabricated with a spherical morphology, a mean size of 289 ± 4.1 nm, and a zeta potential of -13.6 ± 1.1 mV, indicating good stability.In vitrothrombolysis assays demonstrated that PPrC NPs, combined with low-intensity ultrasound (US), exhibited significantly superior thrombolytic efficacy compared with controls (P< 0.05), owing to a synergistic effect of fibrin targeting, US-responsive drug release, and phase-transition enhancement. Cytotoxicity assays on human retinal microvascular endothelial cells confirmed high biocompatibility, with cell viability exceeding 90% at concentrations up to 1000 µg ml^-1. Furthermore, comprehensive hemocompatibility evaluations, including hemolysis, coagulation function, complement activation (C3a), and platelet activation, revealed no adverse effects within the therapeutically relevant concentration range (⩽800 µg ml^-1). Collectively, these findings indicate that the CREKA-modified nanoplatform provides a safe and effective strategy for targeted thrombolysisin vitro, presenting a promising foundation for developing minimally invasive therapies for retinal thrombotic diseases.