Preparation of Nanoparticles Modified by Recombinant Tissue-Type Plasminogen Activator and Its Adoption in Surgical Treatment of Thrombus Targeted Thrombolysis

Abstract

This research aimed to expand the nanomaterial-based drug loading method for the recombinant tissue plasminogen activator (rtPA) treatment of acute phase thrombolysis in ischemic stroke. In this research, the coprecipitation method was used to prepare Fe3O4 magnetic nanomaterials. Polyacrylic acid (PAA) was coated on the surface of the nanomaterials. The nanomaterials were subjected to hydroxyl activation treatment so that it could be connected to rtPA. By EDC/NHSS method, rtPA was covalently attached to the surface of nanomaterials to form a composite nanomaterial that was modified by rtPA, which was FPA-rtPA. Firstly, the material was characterized, then the pharmacokinetics of the material was evaluated. Finally, the thrombus targeting and thrombolytic properties of the material were analyzed. In the experiment, Fe3O4, FPA, PAA, and FPA-PAA were monitored by FT-IR, the peak value of PAA at 1834 cm–1 meant C=O group, and PAA-FPA had a similar peak, each milligram of nanomaterial can be combined with 80.6 μg ± 1.4 μg of rtPA. In the pharmacokinetic test, the half-life of FPA-rtPA was 90 min, which was much higher than the half-life of rtPA in the free state (P < 0.001), so it was suitable as a targeted thrombolytic preparation; the fluorescence intensity of the FPA-rtPA group combined with the fibrin blood clot was significantly stronger than the FPA group, and rtPA-FPA can target fibrin thrombosis in the cerebral thrombosis model. After comparing the postoperative cerebral infarction area, the rtPA-FPA-based group of rats had a significant decrease in cerebral infarction area (P < 0.001), thus the nanomaterials had better thrombolytic properties.