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

Abstract

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 (O2), 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.

In situ synthesized nanozyme for photoacoustic-imaging-guided photothermal therapy and tumor hypoxia relief

“…PB nanozyme is an efficacious PTT agent due to its excellent photothermal properties; 34 , 40 therefore, ISSzyme in the presence of GSH is well suited for tumor-specific PTT. Before studying the anticancer and hypoxia relief effect of ISSzyme in vitro , its biocompatibility was investigated.…”

“…Prussian blue (PB) has been widely investigated as a nanozyme with excellent electrochemical and optical properties. 34 PB nanoparticles have been approved as an antidote for treatment of internal radioactive contamination with thallium and cesium by the United States Food and Drug Administration. 35 In addition, PB nanoparticles can be modified to achieve a variety of functions, for example, it can be used as drug carriers to improve the therapeutic efficacy.…”

“… 36 , 39 PB nanozyme can decompose H 2 O 2 in tumor sites to produce O 2 , so as to relieve tumor hypoxia and inhibit tumor metastasis. 34 , 40 Meanwhile, PB nanozyme can remove excess reactive oxygen species (ROS) from the body to treat ROS-related diseases. 41 Moreover, PB nanoparticles have been widely used as photothermal agents for photothermal therapy (PTT) due to its excellent near-infrared (NIR) absorption and photothermal conversion efficiency.…”

“… 41 Moreover, PB nanoparticles have been widely used as photothermal agents for photothermal therapy (PTT) due to its excellent near-infrared (NIR) absorption and photothermal conversion efficiency. 34 , 38 More importantly, PB nanozyme has been demonstrated to simultaneously relieve inflammation caused by hyperthermia during PTT, thanks to its antioxidative catalytic activity. 42 However, the PB functions are not tumor specific and are therefore “always on”, inducing undesirable side effects during PTT and generating interfering background signals during imaging.…”

Recent advances of CREKA peptide-based nanoplatforms in biomedical applications

“…Zhang et al proposed a comprehensive antithrombotic therapy strategy by integrating non-pharmacological methods such as photothermal therapy (PTT), optical droplet vaporization (ODV), and removal of overexpressed ROS in the thrombotic microenvironment to obtain a more effective antithrombotic therapy (Fig. 6 ) [ 73 ]. In this study, thrombo-specific Prussian blue (PB)-based nanodroplets, namely, PB-PFP@PLGA-CREKA (PB-PFP@PC) nanodroplets, were prepared.…”