Engineering Hyperechogenic Colloids with Clot-Targeting Capabilities from Platelet-Derived Membranes

Thrombosis-related cardiovascular diseases remain the leading global cause of mortality and morbidity. In this study, we present a pioneering approach in the field of nanobiotechnology, 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 characteristics compared to conventional nanoparticles. These 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 <i>in vitro</i> and in live mice <i>in vivo</i>. 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 but instead adhere to preformed platelet-rich <i>in vitro</i> thrombi. Overall, our work showcases the safe and precise utilization of PMBs to directly target acute thrombosis induced by laser injury in murine mesenteric veins <i>in vivo</i>, 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.