The delivery of thrombi-specific nanoparticles incorporating oligonucleotides into injured cerebrovascular endothelium

Biomaterials. 2013 May;34(16):4128-4136. doi: 10.1016/j.biomaterials.2013.02.013. Epub 2013 Mar 5.

Abstract

In acute vascular events, the endothelium derived tissue factor (TF) is the trigger of the coagulation cascade. In this study, EGFP-EGF1 protein-conjugated PEG-PLGA nanoparticle was employed as a TF targeting vehicle, the NF-κB decoy oligonucleotides (ODNs) was incorporated into it and the resulting EGF1-EGFP-NP-ODNs were evaluated as a vector for therapy of cortex infarction. At 2 h after transfection of TF expressed rat brain capillary endothelial cell, EGF1-EGFP-NP-ODNs was more efficiently internalized and located in the cytoplasm than NP-ODNs. At 4 h and 6 h after administration, ODNs were present in the nuclei and obviously inhibited the TF expression. At 6 h after i.v. administration in vivo, most EGF1-EGFP-NP were accumulated in the embolism vessels, distributed in the damaged endothelial cells and lowered the TF expression. At 24 h after i.v. administration, MR imaging of cortex infarcts were predominantly dwindled.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / pathology
  • Cell Death / drug effects
  • Drug Delivery Systems*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / ultrastructure
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology*
  • Fluorescence
  • Gene Expression Regulation / drug effects
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Kinetics
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Nanoparticles / ultrastructure
  • Oligonucleotides / pharmacology*
  • Particle Size
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / metabolism
  • Static Electricity
  • Thromboplastin / genetics
  • Thromboplastin / metabolism
  • Thrombosis / metabolism
  • Thrombosis / pathology*

Substances

  • Oligonucleotides
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Thromboplastin