Thrombosis-related cardiovascular diseases remain the leading global cause of mortality and morbidity. Detection and treatment of these diseases necessitate the use of advanced materials with thrombus-specific targeting capabilities. In this study, we present a pioneering approach in the field of biointerfacing and colloid science, with a focus on clinical translation, aimed at advancing early diagnosis and enhancing treatment options for thrombotic disorders. We introduce the fabrication of platelet membrane-derived bubbles (PMBs), which exhibit distinctive advantageous characteristics for diagnostics and theranostics, as compared to conventional nanoparticles.

PMBs were fabricated via our patented rapid sonication technique [1,2]. Fabricated PMBs possess an average diameter of 700 nm and a negative ζ-potential, mirroring the attributes of parent platelet membranes. Utilizing diagnostic ultrasound imaging, we demonstrated the ability to visualize PMBs as hyperechogenic entities in agarose phantoms in vitro (100- to 400-fold increase in intensity vs buffer control, p < 0.0001). We also visualised and quantified an increase in signal intensity in vivo, in the vessel of mice after intravenous injection (two- to three-fold increase in intensity vs buffer control, p < 0.0001). Furthermore, through confocal laser microscopy, we verified the retention of crucial transmembrane proteins, such as CD41 (GPIIb) and CD42 (GPIb), pivotal in conferring platelet-specific targeting functions. Importantly, our platelet aggregation studies confirmed that PMBs do not induce platelet aggregation, as compared to the platelet agonist thrombin receptor-activating peptide (TRAP, 30 µM) (p < 0.0001). Interestingly, we demonstrated the binding ability of PMBs and their adherence to preformed platelet-rich in vitro thrombi. Furthermore, PMBs are highly compatible with blood and showed no toxicity to cells in vitro, hence these fabricated materials are prospective candidates for further development and application in vivo. Overall, our work showcases the safe and precise utilization of PMBs to directly target acute thrombosis induced by laser injury in murine mesenteric veins in vivo, as visualized through intravital microscopy.

In conclusion, we have successfully developed a rapid method for generating PMBs with unique ultrasound-directed and thrombus-targeting properties. These exceptional attributes of PMBs hold significant promise for advancing the field of ultrasound diagnostic thrombus imaging and clot-targeted therapy in the clinical context.

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Image/Figure Caption:

Representative optical (top left) and transmission electron micrographs (top right) of platelet membrane-derived bubbles (PMBs). Inset shows the dynamic light scattering size distribution of PMBs. Representative sum projections of thrombi formed in intravital laser-induced model of thrombosis before (top middle) and after (top right) intravenous injection of DiIC₁₂‒labelled PMBs. Platelet GPIb shown in purple and PMBs in red. Representative ultrasonograms of mouse inferior vena cava (bottom middle) before and (bottom right) after injection of PMBs.

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