Fibrinogen binding to activated platelets and its biomimetic thrombus-targeted thrombolytic strategies

Int J Biol Macromol. 2024 Aug;274(Pt 1):133286. doi: 10.1016/j.ijbiomac.2024.133286. Epub 2024 Jun 21.

Abstract

Thrombosis is associated with various fatal arteriovenous syndromes including ischemic stroke, myocardial infarction, and pulmonary embolism. However, current clinical thrombolytic treatment strategies still have many problems in targeting and safety to meet the thrombolytic therapy needs. Understanding the molecular mechanism that underlies thrombosis is critical in developing effective thrombolytic strategies. It is well known that platelets play a central role in thrombosis and the binding of fibrinogen to activated platelets is a common pathway in the process of clot formation. Based on this, a concept of biomimetic thrombus-targeted thrombolytic strategy inspired from fibrinogen binding to activated platelets in thrombosis was proposed, which could selectively bind to activated platelets at a thrombus site, thus enabling targeted delivery and local release of thrombolytic agents for effective thrombolysis. In this review, we first summarized the main characteristics of platelets and fibrinogen, and then introduced the classical molecular mechanisms of thrombosis, including platelet adhesion, platelet activation and platelet aggregation through the interactions of activated platelets with fibrinogen. In addition, we highlighted the recent advances in biomimetic thrombus-targeted thrombolytic strategies which inspired from fibrinogen binding to activated platelets in thrombosis. The possible future directions and perspectives in this emerging area are briefly discussed.

Keywords: Activated platelets; Fibrinogen-mimicking nanomedicine; Targeted thrombolytic therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomimetics*
  • Blood Platelets* / drug effects
  • Blood Platelets* / metabolism
  • Fibrinogen* / chemistry
  • Fibrinogen* / metabolism
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Platelet Activation* / drug effects
  • Protein Binding
  • Thrombolytic Therapy / methods
  • Thrombosis* / drug therapy
  • Thrombosis* / metabolism

Substances

  • Fibrinogen
  • Fibrinolytic Agents