title: Development of MRI/NIRF 'activatable' multimodal imaging probe based on iron oxide nanoparticles.
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%.
authors.affiliation: Research Institute of Advanced Materials, Department of Materials Science and Engineering, Seoul National University, San 56-1, Sillim, Gwanak, Seoul 151-744, Republic of Korea.
authors.forename: Eui-Joon
authors.initials: EJ
authors.lastname: Cha
authors.forename: Eue Soon
authors.initials: ES
authors.lastname: Jang
authors.forename: In-Cheol
authors.initials: IC
authors.lastname: Sun
authors.forename: In Joon
authors.initials: IJ
authors.lastname: Lee
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Ko
authors.forename: Young Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage / Q000737:chemistry*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000175:diagnosis / Q000201:enzymology; D011092:Polyethylene Glycols / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D003287:Contrast Media; D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D020778:Matrix Metalloproteinase 2