title: Cytotoxicity, cytocompatibility, cell-labeling efficiency, and in vitro cellular magnetic resonance imaging of gadolinium-catalyzed single-walled carbon nanotubes.
abstract: Cell tracking by magnetic resonance imaging (MRI) is an emerging technique that typically requires the use of MRI contrast agents (CAs). A MRI CA for cellular imaging should label cells efficiently at potentially safe concentrations, have high relaxivity, and not affect the cellular machinery. In this article, we report the cytotoxicity, cytocompatibility, and cell labeling efficiency in NIH/3T3 fibroblasts of novel, single-walled carbon nanotubes synthesized using gadolinium nanoparticles as catalysts (Gd-SWCNTs). Cells incubated with the Gd-SWCNT showed a dose- (50-100 µg/mL nanotube concentration) and time- (12-48 h) dependent decrease in viability. 30% cell death was observed for cells incubated with Gd-SWCNTs at the maximum dose of 100 µg/mL for 48 h. Cells incubated with the Gd-SWCNTs at concentrations between 1-10 μg/mL for 48 h showed no change in viability or proliferation compared to untreated controls. Additionally, at these potentially safe concentrations, up to 48 h, the cells showed no phosphatidyl serine externalization (pre-apoptotic condition), caspase-3 activity (point of no return for apoptosis), genetic damage, or changes in their division cycle. Localization of Gd-SWCNTs within the cells was confirmed by transmission electron microscopy (TEM) and Raman microscopy, and these results show 100% cell labeling efficiency. Elemental analysis also indicates significant uptake of Gd-SWCNTs by the cells (10(8) -10(9) Gd(3+) ions per cell). Finally, T1 -weighted MRI at 3 T of Gd-SWCNT-labelled cells show up to a four-fold increase in MR signal intensities as compared to untreated cells. These results indicate that Gd-SWCNTs label cells efficiently at potentially safe concentrations, and enhance MRI contrast without any structural damage to the cells.
authors.affiliation: Department of Biomedical Engineering, Rm #115, Bioengineering Building, Stony Brook University, Stony Brook, New York 11794-5281.
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Avti
authors.forename: Elisabeth D
authors.initials: ED
authors.lastname: Caparelli
authors.forename: Balaji
authors.initials: B
authors.lastname: Sitharaman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002384:Catalysis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D005682:Gadolinium / Q000494:pharmacology*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008422:Materials Testing; D051379:Mice; D015162:Micronucleus Tests; D041681:NIH 3T3 Cells; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D019047:Phantoms, Imaging; D010718:Phosphatidylserines / Q000378:metabolism; D013059:Spectrum Analysis, Raman; D013194:Staining and Labeling
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers; D037742:Nanotubes, Carbon; D010718:Phosphatidylserines; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3
keywords: Cytotoxicity; MRI contrast agent; gadolinium; labeling efficiencies; single walled carbon nanotubes