Abstract
A thrombus (blood clot) is formed in the injured vessels to maintain the integrity of vasculature. A thrombus, composed mainly of activated platelets and fibrin, obstructs arteries or veins, leading to various life-threatening diseases. During thrombus formation, H 2 O 2 (hydrogen peroxide) is overproduced by activated platelets and other vascular sources and serves as a key mediator of platelet activation and aggregation, facilitating inflammation and development of obstructive vascular diseases. In this regard, high level of H 2 O 2 holds great potential as diagnostic and therapeutic markers of obstructive capsular diseases. Inspired by the distinctive physicochemical characteristics of thrombi such as abundant fibrin and the significant of elevated level of H 2 O 2 , we developed H 2 O 2 -activatable novel nanomedicine (T-FBM) that could detect thrombi through the amplification of ultrasound/photoacoustic signal and serve as an antithrombotic nanomedicine. T-FBM nanoparticles were designed to target fibrin-rich thrombi and be activated by H 2 O 2 to generate CO 2 bubbles to amplify the photoacoustic signal. In the phantom studies, T-FBM nanoparticles showed significant amplification of ultrasound/photoacoustic signals in a H 2 O 2 -triggered manner. T-FBM nanoparticles also exerted H 2 O 2 -activatable antioxidant, anti-inflammatory and antiplatelet activities on endothelial cells. In mouse models of carotid arterial injury, T-FBM nanoparticles significantly enhanced the photoacoustic contrast specifically in thrombosed vessels and significantly suppressed thrombus formation. We anticipate that T-FBM nanoparticles hold great translational potential as nanotheranostics for H 2 O 2 -associated cardiovascular diseases.
Published Version
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