Arterial thrombotic disease is a common and serious clinical medical problem. Nitric oxide (NO), as a therapeutic gas, can delay the progression of thrombosis and reduce tissue ischemia and hypoxia damage. However, systemic delivery of NO causes complications, and NO in the body is easily cleared by hemoglobin in the blood. In this study, we designed a lipid microbubble carrying NO (NO-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) technology to achieve targeted delivery of NO under real-time contrast-enhanced ultrasound monitoring. The good stability of the NO-MBs was demonstrated by examining the changes in diameter, concentration and contrast-enhanced ultrasound intensity with time. Moreover, in vivo and in vitro thrombolysis experiments, it was confirmed that the combination of NO-MBs and UTMD could accelerate arterial thrombolysis. Meanwhile, the levels of inflammatory factors, superoxide dismutase (SOD) and malondialdehyde (MDA) in vascular tissue after treatment were detected, which showed that NO-MBs could significantly reduce the inflammatory response and oxidative stress induced by thromboembolism. In addition, so as to evaluate the safety of the NO-MBs UTMD treatment strategy, MTT assay, hemolysis test, detection of serum biochemical indicators, and H&E staining of major organs were performed. The results showed that this treatment strategy had excellent biosafety. In conclusion, the NO-MBs UTMD treatment strategy has great potential in the treatment of arterial thrombotic diseases.
Keywords: Arterial thrombotic disease; Lipid microbubble; Nitric oxide; Thrombolysis; UTMD.
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