Enhanced cell uptake of superparamagnetic iron oxide nanoparticles functionalized with dendritic guanidines.
Magnetic resonance imaging (MRI) is a powerful tool for the diagnosis of disease and the study of biological processes such as cancer metastasis and inflammation. Superparamagnetic iron oxide (SPIO) nanoparticles have been shown to be effective contrast agents for labeling cells to provide high sensitivity in MRI, but this sensitivity depends on the ability to label cells with sufficient quantities of SPIO, which can be challenging for nonphagocytic cells such as cancer cells. To address this issue, a novel cell-penetrating polyester dendron with peripheral guanidines was developed and conjugated to the surface of SPIO. The functionalized nanoparticles were characterized by transmission electron microscopy, infrared spectroscopy, and dynamic light scattering, and it was found that the surface functionalization reaction proceeded to completion and did not have any adverse effects on the SPIO. In GL261 mouse glioma cells, the dendritic guanidine exhibited remarkably similar cell-penetrating capabilities to the HIV-Tat(47-57) peptide for the transport of fluorescein, and when conjugated to SPIO, it provided significantly enhanced uptake in comparison with nanoparticles having no dendron or dendrons with hydroxyl or amine peripheries. This uptake led to substantial decreases in the transverse relaxation time (T(2)) of labeled cells relative to control cells. While the nanoparticles functionalized with dendritic guanidines exhibited somewhat greater toxicity than those functionalized with dendrons having hydroxyl or amine peripheries, they were still relatively nontoxic at the low concentrations required for labeling.
Martin
Amanda L
AL
Department of Chemistry, The University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada.
Bernas
Lisa M
LM
Rutt
Brian K
BK
Foster
Paula J
PJ
Gillies
Elizabeth R
ER
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D019791:Guanidine / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010455:Peptides / Q000737:chemistry / Q000378:metabolism
D050091:Dendrimers; D005290:Ferric Compounds; D010455:Peptides; C000499:ferric oxide; D019791:Guanidine