Thrombosis‐Responsive Thrombolytic Coating Based on Thrombin‐Degradable Tissue Plasminogen Activator (t‐PA) Nanocapsules

Abstract

Surface modification with bioactive agents capable of combating thrombosis is a widely used strategy for developing antithrombotic biomaterials. However, exposure of the blood to the antithrombotic agent on the material surface may cause hemostatic disorders under normal conditions. Ideally an implanted biomaterial should respond appropriately on demand to a specific change in the physiologic environment, as happens in the body itself. In the present study, a thrombosis-responsive surface coating with the ability to lyse fibrin as it forms is reported. The coating consists of nanocapsules (NCs) in which the fibrinolysis activator t-PA is encapsulated in a thrombin-degradable hydrogel shell. The t-PA NCs are attached to several materials covalently through a polydopamine adhesive layer. The resulting surfaces are treated with the antifouling agent glutathione (GSH) to prevent further interactions with blood/plasma components. The t-PA NCs/GSHcoated surface is stable and remain inert in normal plasma environment while releasing t-PA and promoting fibrinolysis when thrombin is present. The fibrinolytic activity increases with increasing thrombin concentration, and therefore presumably with the extent of thrombosis. This work constitutes the first report of an antithrombotic coating whose function is triggered and regulated, respectively, by the appearance of thrombin and the extent of coagulation.

Inhibition of Inflammation‐Associated Thrombosis with ROS‐Responsive Heparin‐DOCA/PVAX Nanoparticles

“…In addition, the tails of HDP‐treated mice exhibit the similar structure as the normal mice with purple and blue structure dominantly; confirming that pretreatment with HDP‐2 and HDP‐4 nanoparticles restrains the clot formation effectively (Figure e,f). In addition, there is nearly no histological evidence of accumulated toxicity in the different organs after administration of nanoparticles for 3 days (Figure S8, Supporting Information), demonstrating the excellent biocompatibility of HDP nanoparticles . Taken together, we confirmed that the prepared HDP nanoparticles can be employed to treat thrombus associated with inflammation without lethal side effects on hemostasis.…”

Investigation of chitosan‐g‐PEG grafted nanoparticles as a half‐life enhancer carrier for tissue plasminogen activator delivery

“…Entrapped enzyme activity was assayed using a colourimetric method based on S‐2251 substrates [46, 47]. Substrate solution was prepared briefly by adding 1 ml Tris (0.5 M, pH = 7.4) and 5 μl Tween‐20 to 1 ml of 3 mM S‐2251.…”

Advanced functional polymer materials

“…To this end, Chen et al developed a thrombosis-responsive surface coating with the ability to lyse fibrin as it forms. 466,467 Thrombin generation is a key event in blood coagulation/thrombosis and therefore has been used as a physiologic stimulus or trigger in the design of this coating. As shown in Fig.…”