title: Silica- and alkoxysilane-coated ultrasmall superparamagnetic iron oxide particles: a promising tool to label cells for magnetic resonance imaging.
abstract: In this study silica- and alkoxysilane-coated ultrasmall superparamagnetic iron oxide (USPIO) particles were synthesized, and their ability to label immortalized progenitor cells for magnetic resonance imaging (MRI) was compared. USPIO particles were synthesized by coprecipitation of ferric and ferrous salts. Subsequently, the particles were coated with silica, (3-aminopropyl)trimethoxysilane (APTMS), and [N-(2-aminoethyl)-3-aminopropyl]trimethoxysilane (AEAPTMS). The size of the USPIO particles was about 10 nm without a significant increase in diameter after coating. The highest T2 relaxivity was achieved for silica-coated USPIO particles, 339.80 +/- 0.22 s-1 mM-1, as compared with APTMS- and AEAPTMS-coated ones, reaching 134.40 +/- 0.01 and 84.79 +/- 0.02 s-1 mM-1, respectively. No toxic effects on the cells could be detected by trypan blue, TUNEL, and MTS assays. Uptake of USPIO particles was evaluated by Prussian blue staining, transmission electron microscopy, T2-MR relaxometry, and mass spectrometry. It was found that cell uptake of the different USPIO particles increased for longer incubation times and higher doses. Maximum cellular iron concentrations of 42.1 +/- 4.0 pg/cell (silica-coated USPIO particles), 37.1 +/- 3.5 pg/cell (APTMS-coated USPIO particles), and 32.7 +/- 4.0 pg/cell (AEAPTMS-coated USPIO particles) were achieved after incubation of the cells with USPIO particles at a dose of 3 micromol/mL for 6 h. The decrease of the T2 relaxation time of the cell pellets was most pronounced for cells incubated with silica-coated USPIO particles followed by APTMS- and AEAPTMS-coated particles, respectively. In gelatin gels even small clusters of labeled cells were detected by 1.5 T MRI, and significant changes in the T2 relaxation times of the gels were determined for 10000 labeled cells/mL for all particles. In summary, as compared with APTMS- and AEAPTMS-coated particles, silica-coated USPIO particles provide the highest T2 relaxivity and most effectively reduce the T2 relaxation time of immortalized progenitor cells after internalization. This suggests silica-coated USPIO particles are most suited for cell labeling approaches in MRI.
authors.affiliation: Junior Group Molecular Imaging and Departments of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Zhang
authors.forename: Björn
authors.initials: B
authors.lastname: Wängler
authors.forename: Bernd
authors.initials: B
authors.lastname: Morgenstern
authors.forename: Hanswalter
authors.initials: H
authors.lastname: Zentgraf
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.forename: Harald
authors.initials: H
authors.lastname: Untenecker
authors.forename: Ralf
authors.initials: R
authors.lastname: Krüger
authors.forename: Ralf
authors.initials: R
authors.lastname: Huss
authors.forename: Christian
authors.initials: C
authors.lastname: Seliger
authors.forename: Wolfhard
authors.initials: W
authors.lastname: Semmler
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D005290:Ferric Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D005782:Gels; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D012821:Silanes; D012822:Silicon Dioxide; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; D005782:Gels; D012821:Silanes; C000499:ferric oxide; D012822:Silicon Dioxide