Molecularly Engineered Theranostic Nanoparticles for Thrombosed Vessels: H₂O₂-Activatable Contrast-Enhanced Photoacoustic Imaging and Antithrombotic Therapy

Abstract

A thrombus (blood clot), composed mainly of activated platelets and fibrin, obstructs arteries or veins, leading to various life-threatening diseases. Inspired by the distinctive physicochemical characteristics of thrombi such as abundant fibrin and an elevated level of hydrogen peroxide (H₂O₂), we developed thrombus-specific theranostic (T-FBM) nanoparticles that could provide H₂O₂-triggered photoacoustic signal amplification and serve as an antithrombotic nanomedicine. T-FBM nanoparticles were designed to target fibrin-rich thrombi and be activated by H₂O₂ to generate CO₂ bubbles to amplify the photoacoustic signal. In the phantom studies, T-FBM nanoparticles showed significant amplification of ultrasound/photoacoustic signals in a H₂O₂-triggered manner. T-FBM nanoparticles also exerted H₂O₂-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 H₂O₂-associated cardiovascular diseases.