Nitric Oxide-Loaded Nanobubbles for the Treatment\nof Acute Pulmonary Embolism and Mitigation of Lung Ischemia–Reperfusion\nInjury

Acute\npulmonary embolism (APE) is a life-threatening complication\nthat is primarily caused by the migration of deep vein thrombosis\nto the lungs. However, current drug treatments have limited efficacy\nand can lead to lung ischemia–reperfusion injury (LIRI) after\nthrombolysis. Inhaled nitric oxide has shown potential for APE therapy,\nbut its clinical feasibility is still uncertain. In this study, nitric\noxide (NO) was directly encapsulated by nanobubbles to form NO-loaded\nnanobubbles (NanoNO) as a potential treatment for APE and subsequent\nLIRI. NanoNO, with a size of 219.27 ± 2.42 nm and a polydispersity\nindex of 0.17, could encapsulate up to 1.1 mM NO. In the LIRI cell\nmodel, NanoNO increased NO concentration and superoxide dismutase\n(SOD) enzyme activities while reducing reactive oxygen species (ROS)\nand malondialdehyde (MDA) levels (2.80-fold), leading to decreased\ncell apoptosis. In a rabbit model of APE, NanoNO was compared to sodium\nnitroprusside (SNP, a positive control) for thrombolysis efficacy\nby using blood gas analysis, pulmonary angiography, echocardiography,\nand hematoxylin–eosin staining. The results demonstrated that\nNanoNO was more effective than SNP in thrombolysis, as evidenced by\nits better ability to remove blood clots, normalize pulmonary arteries,\nand relieve right ventricular (RV) dilatation. In the LIRI rabbit\nmodel, NanoNO decreased serum MDA, tumor necrosis factor-α (TNF-α),\nand interleukin-6 (IL-6) while increasing serum SOD. Collectively,\nthese findings highlight the potential of NanoNO as a promising therapeutic\napproach for the treatment of APE and the mitigation of LIRI.