Multimodal SPION-CREKA peptide based agents for molecular imaging of microthrombus in a rat myocardial ischemia-reperfusion model

Biomaterials. 2014 Mar;35(9):2961-70. doi: 10.1016/j.biomaterials.2013.12.038. Epub 2014 Jan 3.

Abstract

Microthrombosis plays a key role in many cardiovascular diseases. Although it is not difficult to localize thrombus within large or middle-sized vessels, the noninvasive diagnostic regimen for the detection of microthrombus remains scarce. Here we developed a nanoagent by conjucting superparamagnetic iron-oxide nanoparticle with fluorophore and a targeting element, CREKA, a peptide with special affinity for fibrin. In a rat model of myocardial ischemia-reperfusion (MI/R), the multimodal nanoagents were readily and selectively accumulated within microthrombosis, which was detectable by both magnetic resonance and optical imaging modalities. The fibrin-targeted nanoagent could be expected to have utility not only in molecular imaging of fibrin, understanding the mechanisms of microcirculation disorders, but also in targeted therapy with fibrinolytic agents.

Keywords: Fibrin; Magnetic resonance imaging; Microthrombosis; Multimodal nanoagents; Optical imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Coagulation / drug effects
  • Blood Platelets / drug effects
  • Blood Platelets / pathology
  • Blood Platelets / ultrastructure
  • Dextrans*
  • Disease Models, Animal
  • Humans
  • Magnetite Nanoparticles*
  • Male
  • Microscopy, Fluorescence
  • Molecular Imaging / methods*
  • Multimodal Imaging / methods*
  • Myocardial Reperfusion Injury / complications
  • Myocardial Reperfusion Injury / diagnosis*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Oligopeptides* / pharmacology
  • Optical Imaging
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley
  • Static Electricity
  • Thrombosis / complications*
  • Thrombosis / diagnosis*

Substances

  • Dextrans
  • Magnetite Nanoparticles
  • Oligopeptides
  • cysteinyl-arginyl-glutamyl-lysyl-alanyl
  • ferumoxides