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

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 12 h 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 12 h post injection of PCM-CS. The maximum signal difference between tumor region and healthy muscle was 34%.