CARS microscopy for the visualization of micrometer-sized iron oxide MRI contrast agents in living cells

Abstract

Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.

Coherent anti-Stokes Raman scattering enhancement of thymine adsorbed on graphene oxide

“…The enhancement of CARS signal for molecules localized on nanostructured gold surface with an enhancement factor of approximately 10 5 was published in [ 17 ]. It was also established that this method is attractive for visualization of macromolecules and cell components [ 19 ].…”

Intracellular imaging of quantum dots, gold, and iron oxide nanoparticles with associated endocytic pathways

“…However, MRI only provides a low resolution at 0.5 mm in general . Recently, CARS microscopy was invented as a novel technique to detect SPIONs because of its high spatial resolution from 300 nm to 1 μm and can easily be detected from intracellular SPIONs from the background . Other than MRI signal, IONP have been recognized as a PA contrast agent.…”

“…54 Recently, CARS microscopy was invented as a novel technique to detect SPIONs because of its high spatial resolution from 300 nm to 1 μm and can easily be detected from intracellular SPIONs from the background. 55 Other than MRI signal, IONP have been recognized as a PA contrast agent. Kanazaki et al conjugated the HER2 antibody on IONP, enabling NP to bind specifically on cells with HER2 expression on the cell surface then HER2-positive tumors were observed under PA imaging.…”

Personalized nanomedicine advancements for stem cell tracking

“…Coherent anti-Stokes Raman scattering (CARS) microscopy enables the visualization of metal oxide particles based only on their electron density, obviating the need for combination with other labels for in vitro visualization [293,294]. Further advances with the application of stimulated Raman scattering provides such visualization at high temporal resolution, enabling recording at video-rate [295].…”