title: Release activation of iron oxide nanoparticles: (REACTION) a novel environmentally sensitive MRI paradigm.
abstract: Smart contrast agents for MRI-based cell tracking would enable the use of MRI methodologies to not only detect the location of cells but also gene expression. Here, we report on a new enzyme/contrast agent paradigm which involves the enzymatic degradation of the polymer coating of magnetic nanoparticles to release encapsulated magnetic cores. Cells were labeled with particles coated with a polymer, which is cleavable by a specific enzyme. This coat restricts the approach of water to the particle, preventing the magnetic core from efficiently relaxing protons. The reactive enzyme was delivered to cells and changes in cellular T(2) and T(2)* relaxation times of ~ 35% and ~ 50% were achieved in vitro. Large enhancements of dark contrast volume (240%) and contrast-to-noise ratio (48%) within the contrast regions were measured, in vivo, for cells co-labeled with enzyme and particles. These results warrant exploration of genetic avenues toward achieving release activation of iron oxide nanoparticles.
authors.affiliation: Molecular and Cellular MRI Laboratory, Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Dorit
authors.initials: D
authors.lastname: Granot
authors.forename: Erik M
authors.initials: EM
authors.lastname: Shapiro
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000378:metabolism; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism*; D003910:Dextranase / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D003910:Dextranase; C065507:ferumoxides