Abstract
AbstractFormation of an occlusive thrombus is a critical pathophysiological feature of numerous cardiovascular diseases. Thrombosis is promoted by P‐selectin overexpressed on activated platelets and endothelium and tightly linked with the overproduction of hydrogen peroxide (H2O2). The overexpression of P‐selectin and overproduction of H2O2 become unique features of thrombosed vessels which provide a rationale for the development of targeted therapeutics for thrombosis. In this work, targeted self‐delivering and H2O2‐activatable antithrombotic nanomedicine (Fu–sBR) composed of a self‐immolative dimeric prodrug (sBR) and a P‐selectin targeting fucoidan, are reported. In the presence of fucoidan, sBR is formulated into stable nanoassemblies that can serve as carrier‐free nanodrugs and exert antioxidant, anti‐inflammatory, and antiplatelet activities in a H2O2‐triggered manner. In mouse models of carotid arterial thrombosis and deep vein thrombosis (DVT), Fu–sBR nanoassemblies specifically target thrombosed vessels to effectively suppress thrombus development by inhibiting the expression of tumor necrosis factor‐alpha (TNF‐α), interleukine‐1 beta (IL‐1β), and soluble CD40 ligand (sCD40L). Given their self‐delivering capability, thrombus targeting ability, and stimulus‐activatable therapeutic actions, Fu–sBR nanoassemblies have great translational potential as therapeutic agents for various thrombotic disorders.
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