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H2O2-triggered “off/on signal” nanoparticles target P-selectin for the non-invasive and contrast-enhanced theranostics for arterial thrombosis

Ying Wang,Chuanjiang Jian,Yiqing Long,Xiaowen Xu,Yang Song,Zongning Yin

Pathological coagulation within an injured artery and the subsequent cardiovascular complications, such as stroke and heart attack, greatly threaten human life. Inspired by the biochemical features of acute arterial thrombosis, such as abundant activated platelets and hydrogen peroxide (H 2 O 2 ), we constructed platelet-targeted theranostic nanoparticles (CyBA/PFM NPs) with H 2 O 2 -triggered photoacoustic contrast enhancement and antithrombotic capabilities. CyBA/PFM NPs were designed to target platelet-rich clots via fucoidan segment within the carrier, which could be activated by H 2 O 2 to produce fluorescent “CyOH” molecules, thus turning on the photoacoustic signal. CyBA/PFM NPs showed obvious amplification of fluorescence following incubation with fresh clots, exhibiting efficient scavenging ability of intracellular reactive oxygen species (ROS). In a FeCl 3 -induced mouse model of carotid thrombosis, CyBA/PFM NPs significantly amplified the photoacoustic contrast in thrombogenic tissues, effectively eliminated ROS within the occlusion site, and suppressed the thrombus formation , accompanied by a normalization of the soluble CD40L level. Given their accurate imaging potential, potent antithrombotic activities and acceptable biosafety, CyBA/PFM NPs hold strong potential as nanoscale theranostics for H 2 O 2 -correlated cardiovascular diseases. Statement of significance In this study, we developed a platelet-targeted and H 2 O 2 -triggered nanosystem self-assembled from phenylboronated fucoidan/maltodextrin polymers and responsive near-infrared probes. The fucoidan segment within the carrier could facilitate the specific delivery of the therapeutic polymers and probes to the platelet-rich arterial thrombus. In a mouse model of FeCl 3 -induced arterial thrombosis, the system could be activated by H 2 O 2 to produce fluorescent “CyOH” molecules, thus turning on the photoacoustic signal and specifically imaging thrombosed tissues. Besides, CyBA/PFM NPs significantly effectively eliminated ROS within the occlusion site and suppressed the thrombus formation. Given their theranostic potential and acceptable biosafety, this system has great potential for H 2 O 2 -correlated cardiovascular diseases.