Precise thrombolysis in-vivo and in-vitro study on improved MnO2-loaded pep'-Fuco nanocarriers

Background: Venous thrombosis is the main cause of incidence rate and mortality of cardiovascular diseases worldwide. The current thrombolytic therapy often faces systemic side effects, limited targeting, and adverse hypoxic microenvironment adjustments within the thrombus, which may impair efficacy. Objective: The goal is to investigate the thrombolytic effect of MnO2@pep'-Fuco needle on venous thrombosis in both in-vivo and in-vitro environments. Methods: In this study, we have injected rats with PBS, MnO2@pep-Fuco, free uPA, MnO2-COOH/uPA, MnO2/uPA@pep-Fuco and MnO2/uPA@pep'-Fuco and then we have measured their vascular occlusion rate, haemolysis, body weight and the biochemical profile of plasma. Results: The study systematically evaluates the thrombolytic performance of MnO2@pep'-Fuco nanoparticles and it is observed that these flower-shaped nanoparticles have a pep-Fuco grafting rate of 3.87%. They can release 23.2% of dissolved oxygen within 25 minutes and achieve 90.5% drug release rate within 50 hours. The nanoparticles also exhibit excellent biocompatibility, with a cell death rate of 1.26% and red blood cell adhesion rate of 90%. In-vivo experiments, a complete thrombolysis (100%) has been achieved with a thrombus-to-vein fluorescence intensity ratio of 2:7. The study reveals excellent biosafety, with a hemolysis rate of 0.65 to 0.82% without any significant changes in body weight. Conclusion: These results indicate that the MnO2/uPA@pep-Fuco nanoparticle system is a promising novel therapeutic strategy for treating venous thrombosis with great efficacy.