Platelet membrane-camouflaged bioactive glass nano-formulations for enhanced drug delivery in the treatment of acute arterial thrombosis.

Abstract

Thrombus treatment remains a significant challenge, primarily due to factors such as the short half-life of thrombolytic agents, suboptimal drug utilization, and limited therapeutic efficacy. In this study, we developed a platelet membrane-camouflaged bioactive glass nanoparticles (BGs) as drug carriers to load thrombolytic agent urokinase (UK) and anticoagulant drug tirofiban (TF). UK and TF were firstly incorporated onto BGs, and followed by a camouflage of polydopamine (PDA) and platelet membrane (PM) to form composite nano-formulation (TUBGs@PP). This composite nano-formulation leverages the PM camouflage to enhance its biocompatibility, prolong circulation time in vivo, and extend the half-life of drugs. Additionally, as-fabricated TUBGs@PP composite nano-formulation can circumvent immune system-mediated clearance, thereby facilitating targeted drug delivery to the thrombus sites and enhancing the thrombolytic efficacy. In vivo results demonstrated that the TUBGs@PP composite nano-formulations not only prolonged circulation time but also effectively unclogged blood vessels at the site of thrombosis, while reducing recurrence of thrombosis and drug side effects. STATEMENT OF SIGNIFICANCE: The platelet membrane-camouflaged bioactive glass nanoparticles as drug carriers for the synergistic co-delivery of urokinase and tirofiban have been developed (TUBGs@PP) for the treatment of acute arterial thrombosis. This cutting-edge therapeutic strategy addresses several critical limitations inherent in current thrombolytic treatments, including the transient half-life of thrombolytic agents, suboptimal drug bioavailability, and limited therapeutic efficacy. In vivo studies demonstrate that TUBGs@PP not only achieves sustained circulation but also effectively restores vascular patency at thrombotic loci, concurrently reducing the risk of thrombotic recurrence and minimizing adverse drug effects. This study highlights the paradigm-shifting potential of TUBGs@PP in thrombolytic therapy, offering a transformative solution to existing challenges and promising to markedly improve clinical outcomes for patients.