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.

Keywords: platelet membrane; dopamine; urokinase; tirofiban; thrombosis; bioactive glass