Recombinant Plasminogen Activator Modified Nanoparticles for Targeting Thrombolysis in Branch Retinal Vein Occlusion

Cell Mol Biol (Noisy-le-grand). 2022 Mar 31;68(3):201-212. doi: 10.14715/cmb/2022.68.3.23.

Abstract

Branch Retinal Vein Occlusion (BRVO) is the second chronic branch retinal vascular disease that causes abnormal vision loss after acute branch retinal disease in type 2 diabetes. There is no scientific conclusion about its specific pathogenic mechanism at present. Most clinical scholars generally support the theory that the partial human anatomical structure and various systemic risk psychological factors cause insufficient oxygen supply and hemostasis in the local branch retinal arteries. The research results of this article aim to reconstruct a non-nanocell-targeted thrombolytic drug delivery system without modification of rtPA without polyethylene glycol-methyl polycaprolactone and to re-evaluate its thrombus targeting and dissolution. The effect and safety of thrombus provide a new strategy for realizing combined treatment of thrombus. It is a study on the targeting of rtPA-NP to thrombus and its thrombolytic properties. HPLC method was used to detect the binding of fibrin clot prepared in vitro with coumarin-6 labeled NP and rtPA-NP; immunofluorescence technique was used to observe the location of nanomedicine and fibrin clot in branch retinal vein occlusion model Condition. The rtPA-NP drug delivery system constructed in this study not only retains the activity of rtPA and good thrombus targeting but also significantly prolongs its half-life and simplifies the way of administration. The therapeutic efficiency of rtPA-NP thrombus targeted administration on branch retinal vein occlusion reached 85.64%. The successful construction of the rtPA-NP thrombus targeted drug delivery system provides a new way for thrombosis treatment and lays the foundation for the future combination of anticoagulants and vascular protection drugs to achieve the combined treatment of thrombosis and the development of safe and efficient thrombolytic drugs.

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Fibrin / metabolism
  • Fibrin / therapeutic use
  • Fibrinolytic Agents / chemistry
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Nanoparticles* / chemistry
  • Nanoparticles* / therapeutic use
  • Recombinant Proteins / therapeutic use
  • Retinal Vein Occlusion* / drug therapy
  • Thrombolytic Therapy
  • Thrombosis* / pathology
  • Tissue Plasminogen Activator* / chemistry
  • Tissue Plasminogen Activator* / therapeutic use

Substances

  • Fibrinolytic Agents
  • Recombinant Proteins
  • Fibrin
  • Tissue Plasminogen Activator