Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells

Abstract

A promising new direction for contrast-enhanced magnetic resonance (MR) imaging involves tracking the migration and biodistribution of superparamagnetic iron oxide (SPIO)-labeled cells in vivo. Despite the large number of cell labeling studies that have been performed with SPIO particles of differing size and surface charge, it remains unclear which SPIO configuration provides optimal contrast in non-phagocytic cells. This is largely because contradictory findings have stemmed from the variability and imprecise control over surface charge, the general need and complexity of transfection and/or targeting agents, and the limited number of particle configurations examined in any given study. In the present study, we systematically evaluated the cellular uptake of SPIO in non-phagocytic T cells over a continuum of particle sizes ranging from 33 nm to nearly 1.5 μm, with precisely controlled surface properties, and without the need for transfection agents. SPIO labeling of T cells was analyzed by flow cytometry and contrast enhancement was determined by relaxometry. SPIO uptake was dose dependent and exhibited sigmoidal charge dependence, which was shown to saturate at different levels of functionalization. Efficient labeling of cells was observed for particles up to 300nm, however micron-sized particle uptake was limited. Our results show that an unconventional highly cationic particle configuration at 107 nm maximized MR contrast of T cells, outperforming the widely utilized USPIO (<50 nm).

Synthesis, Characterization, and Toxicity Evaluation of Dextran-Coated Iron Oxide Nanoparticles

“…The study of Thorek and Tsourkas [54] with dextran-iron oxide nanoparticles of different diameters has shown that these were fully soluble at physiological conditions and efficiently internalized up to a size of 100 nm. For all dimensions, the saturating level was reached at a cellular iron concentration below 50 µg/mL.…”

Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles

“…The concentration and the charge play a significant role in the cellular internalization [25]. For instance, negatively charged fluorescently labeled SPIONs have a higher internalization in prostate-cancer PC-3 cell line as observed via confocal microscopy or flow cytometry, in comparison to positively charged SPIONs [26].…”

Altering the response of intracellular reactive oxygen to magnetic nanoparticles using ultrasound and microbubbles

“…The exact mechanism of the biotoxicity of nanosized iron oxides is an ongoing discussion; the most likely causes include size, concentration, and chemical surface modification, as well as incubation time [39]. Voinov et al [40] reported that γ-Fe 2 O 3 nanoparticles 20-40 nm in diameter could mediate the production of highly reactive hydroxyl radicals because an increase in the intracellular free iron level affected the normal ROS-antioxidant balance by promoting ROS production.…”