Antithrombotic Therapy by Regulating the ROS-Mediated Thrombosis Microenvironment and Specific Nonpharmaceutical Thrombolysis Using Prussian Blue Nanodroplets.

In thrombotic diseases, the effects of reactive oxygen species (ROS)-mediated oxidative stress as a "perpetrator" in thrombosis must be resolved. Accordingly, an insufficient understanding of thrombus therapy prompted the authors to pursue a more comprehensive and efficient antithrombotic treatment strategy. A Prussian blue (PB)-based nanodroplet system (PB-PFP@PC) is designed using PB and perfluorinated pentane (PFP) in the core, and a targeting peptide (CREKA, Cys-Arg-Glu-Lys-Ala) is attached to poly(lactic-coglycolic acid) (PLGA) as the delivery carrier shell. Upon near-infrared (NIR) laser irradiation, PB and PFP jointly achieve an unprecedented dual strategy for drug-free thrombolysis: photothermal therapy (PTT) combined with optical droplet vaporization (ODV). PB, a nanoenzyme, also regulates the vascular microenvironment via its antioxidant activity to continuously scavenge abnormally elevated ROS and correspondingly reduce inflammatory factors in the thrombus site. This study provides a demonstration of not only the potential of ODV in thrombus therapy but also the mechanism underlying PTT thrombolysis due to thermal ablation-induced fibrin network structural damage. Moreover, PB catalyzes ROS to generate oxygen (O 2 ), which combines with the ODV effect, enhancing the ultrasound signal. Thus, regulation of the thrombosis microenvironment combined with specific nonpharmaceutical thrombolysis by PB nanodroplets provides a more comprehensive and efficient antithrombotic therapeutic strategy.