Development of MRI/NIRF 'activatable' multimodal imaging probe based on iron oxide nanoparticles

J Control Release. 2011 Oct 30;155(2):152-8. doi: 10.1016/j.jconrel.2011.07.019. Epub 2011 Jul 23.

Abstract

A fabrication method of Cy5.5-MMP substrate and PEG conjugated iron oxide nanoparticles with thin silica coating (PCM-CS) and its potential as an 'activatable' dual imaging probe for tumor imaging is described in this report. PCM-CS showed an intensity-averaged diameter of 43.1 ± 6.3 nm by dynamic light scattering without any noticeable aggregation over 7 days. Fluorescence of Cy5.5 on the surface of nanoparticles was fully quenched and the quenching efficiency was 97.2%. PCM-CS showed protease specific fluorescence recovery in vitro caused from the specific peptide cleavage by MMP-2 and the probe displayed the sensitivity on 0.5 nM or less enzyme concentration. Tumor was successfully visualized by NIRF and MRI in vivo by intravenously injected PCM-CS. NIRF signal of tumor was gradually increased up to 12h post injection and the intensity of tumor was about 3-4 times higher than normal tissue. NIRF signal at MMP-2 inhibitor treated tumor was clearly lower than tumor without inhibitor due to the insufficient peptide cleavage. NIRF signal at excised tumor was 5-10 times stronger than other organs. Noticeable darkening in magnetic resonance image was observed at the tumor region and the image was gradually darkened at 12h post injection of PCM-CS. The maximum signal difference between tumor region and healthy muscle was 34%.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbocyanines / administration & dosage
  • Carbocyanines / chemistry*
  • Cell Line, Tumor
  • Contrast Media / administration & dosage
  • Contrast Media / chemistry*
  • Magnetic Resonance Imaging*
  • Magnetite Nanoparticles / chemistry*
  • Matrix Metalloproteinase 2 / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neoplasms, Experimental / diagnosis
  • Neoplasms, Experimental / enzymology
  • Polyethylene Glycols / chemistry*
  • Silicon Dioxide / chemistry
  • Spectroscopy, Near-Infrared*

Substances

  • CY5.5 cyanine dye
  • Carbocyanines
  • Contrast Media
  • Magnetite Nanoparticles
  • Polyethylene Glycols
  • Silicon Dioxide
  • Matrix Metalloproteinase 2