Abstract
A thrombus, known as a blood clot, may form within the vascular system of the body and impede blood flow. Thrombosis is the most common underlying pathology of cardiovascular diseases, contributing to high morbidity and mortality. However, the main thrombolytic drugs (urokinase, streptokinase, etc.) have shortcomings, including a short half-life, serious side effects and a lack of targeting, that limit their clinical application. The use of nano-drug delivery systems is expected to address these problems and a variety of approaches, including biological and physical responsive systems, have been explored. In this report, recent advances in the development of targeted nano-drug delivery systems are thoroughly reviewed.
Highlights
Blood plays indispensable roles that include the transportation of oxygen and nutrients, removal of waste products, regulation of body temperature and defense against infection
Arterial thrombosis is highly dependent on the state of the vessel wall, platelets and factors related to blood flow
Arterial thrombosis typically develops in an environment characterized by much higher shear stress and blood flow than in the venous system (i.e., 3.0–26 vs. 1.2–4.8 mL/min) [25]
Summary
Blood plays indispensable roles that include the transportation of oxygen and nutrients, removal of waste products, regulation of body temperature and defense against infection. Thrombolytic agents used to treat arterial thrombosis are antiplatelet drugs, while drugs targeting clotting factors in the coagulation cascade are used to treat venous thromboembolism. Second-generation (tPA) and third-generation agents (TNK-tPA and reteplase) exhibit an affinity for fibrin [4] These drugs have disadvantages, such as low bioavailability, off-target side effects, limited penetration of thrombi and an increased risk of uncontrolled bleeding [5]. Collagen beneath the vascular endothelium is exposed, which activates platelets and enables the release of coagulation factor XII, promoting endogenous coagulation. The conditions for venous thrombosis are summed up in Virchow’s triangle theory: cardiovascular endothelial cell injury, changes in blood flow and hypercoagulability of blood [3]. Neutrophils release DNA fibers within the cell in an inflammatory environment, stimulating thrombosis [11]
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