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

• Published in: Journal of controlled release 2011-10, Vol.155 (2), p.152-158
• Main Authors: Cha, Eui-Joon, Jang, Eue Soon, Sun, In-Cheol, Lee, In Joon, Ko, Jeong Hoon, Kim, Young Il, Kwon, Ick Chan, Kim, Kwangmeyung, Ahn, Cheol-Hee
• Format: Article
• Language: English
• Subjects: Activatable; Animals; Biological and medical sciences; Carbocyanines - administration & dosage; Carbocyanines - chemistry; Cell Line, Tumor; coatings; Contrast Media - administration & dosage; Contrast Media - chemistry; Core-shell nanoparticle; Dual imaging; fluorescence; General pharmacology; image analysis; intravenous injection; Iron oxide; iron oxides; light scattering; Magnetic Resonance Imaging; Magnetite Nanoparticles - chemistry; Matrix Metalloproteinase 2 - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; MRI; muscles; nanoparticles; Neoplasm Transplantation; Neoplasms, Experimental - diagnosis; Neoplasms, Experimental - enzymology; Optical imaging; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylene Glycols - chemistry; proteinases; silica; Silicon Dioxide - chemistry; Spectroscopy, Near-Infrared
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2011.07.019

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%. [Display omitted]