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.

• Authors: Wenli Zhang, Junrui Wang, Zhuoyan Xie, Hongmi Zou, Qiaoqi Chen, Lian Xu, Liu Hu, Ni Fang, Jie Xu, Jun Zhou, Jia Liu, Haitao Ran, Zhigang Wang, Yu Zhang, Dajing Guo
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 18 Issue 15 Pg. e2106252 (04 2022) ISSN: 1613-6829 [Electronic] Germany
• PMID: 35246943 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Wiley-VCH GmbH.

Chemical References

• Ferrocyanides
• Fibrinolytic Agents
• Reactive Oxygen Species
• ferric ferrocyanide

Topics

• Ferrocyanides
• Fibrinolytic Agents (pharmacology, therapeutic use)
• Humans
• Nanoparticles (chemistry)
• Reactive Oxygen Species
• Thrombolytic Therapy
• Thrombosis (therapy)