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Iron oxide nanoparticle internalization exerts detrimental effects on cell physiology for a variety of particles, but little is known about the mechanism involved. The effects of high intracellular levels of four types of iron oxide particles (Resovist, Endorem, very small organic particles, and magnetoliposomes (MLs)) on the viability and physiology of murine C17.2 neural progenitor cells and human blood outgrowth endothelial cells are reported. The particles diminish cellular proliferation and affect the actin cytoskeleton and microtubule network architectures as well as focal adhesion formation and maturation. The extent of the effects correlates with the intracellular concentration (= iron mass) of the particles, with the biggest effects for Resovist and MLs at the highest concentration (1000 microg Fe mL(-1)). Similarly, the expression of focal adhesion kinase (FAK) and the amount of activated kinase (pY397-FAK) are affected. The data suggest that high levels of perinuclear localized iron oxide nanoparticles diminish the efficiency of protein expression and sterically hinder the mature actin fibers, and could have detrimental effects on cell migration and differentiation.

Iron oxide nanoparticles (NPs) are frequently employed in biomedical research as magnetic resonance (MR) contrast agents where high intracellular levels are required to clearly depict signal alterations. To date, the toxicity and applicability of these particles have not been completely unraveled. Here, we show that endosomal localization of different iron oxide particles results in their degradation and in reduced MR contrast, the rate of which is governed mainly by the stability of the coating. The release of ferric iron generates reactive species, which greatly affect cell functionality. Lipid-coated NPs display the highest stability and furthermore exhibit intracellular clustering, which significantly enhances their MR properties and intracellular persistence. These findings are of considerable importance because, depending on the nature of the coating, particles can be rapidly degraded, thus completely annihilating their MR contrast to levels not detectable when compared to controls and greatly impeding cell functionality, thereby hindering their application in functional in vivo studies.

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The adsorption of different types of phosphatidylglycerols onto magnetizable solid particles is studied. The super-paramagnetic magnetite spheres used have an average diameter of only 14 nm and are stabilized by lauric acid to keep them in solution. During incubation and dialysis of this water-based magnetic fluid in the presence of preformed sonicated phospholipid vesicles, magnetoliposomes are formed which are captured from solution with high efficiency by high-gradient magnetophoresis. Support for the bilayer character of the phospholipid coat is derived from both theoretical calculations and experimental data. Phospholipids which form the inner monolayer are adsorbed very quickly with their charged head-group orientated towards the iron oxide surface. The high-affinity character of the binding is reflected in the adsorption isotherms and is further illustrated by their non-extractability with high concentrations of Tween 20. The outer layer assembles through interaction with the exposed hydrocarbon chains. As compared to the inner layer, the phospholipids adsorb at a much slower rate and are displaced by Tween 20 concentrations which usually disrupt conventional membranes. The adsorption isotherms for this layer obey the Langmuir expression. The affinity constants, derived from them, progressively increase as the hydrophobic nature of the phosphatidylglycerols is more pronounced.

Iron oxide nanoparticles are the most widely used T(2)/T(2)* contrast agents and for biomedical research purposes, one of the main applications is the in vitro labeling of stem or therapeutic cells, allowing them to be subsequently tracked in vivo upon transplantation. To allow this, the nanoparticles used should not show any sign of cytotoxicity and not affect cellular physiology as this could impede normal cell functionality in vivo or lead to undesired side-effects. Assessing the biocompatibility of the nanoparticles has proven to be quite a difficult task. In the present work, a small overview of commonly used assays is presented in order to assess several aspects, such as cell viability, induction of reactive oxygen species, nanoparticle uptake, cellular morphology, cellular proliferation, actin cytoskeleton architecture and differentiation of stem cells. The main focus is on comparing the advantages and disadvantages of the different assays, highlighting several common problems and presenting possible solutions to these problems as well as pointing out the high importance of the relationship between intracellular nanoparticle concentration and cytotoxicity.

The in vitro labeling of stem or therapeutic cells with engineered nanoparticles with the aim of transplanting these cells into live animals and, for example, noninvasively monitoring their migration, is a hot topic in nanomedicine research. It is of crucial importance that cell-nanoparticle interactions are studied in depth in order to exclude any negative effects of the cell labeling procedure. To date, many disparate results can be found in the literature regarding nanoparticle toxicity due to the great versatility of different parameters investigated. In the present work, an overview is presented of different types of nanomaterials, focusing mostly on iron oxide nanoparticles, developed for biomedical research. The difficulties in assessing nanoparticle-mediated toxicity are discussed, an overview of some of the problems encountered using commercial (dextran-coated) iron oxide nanoparticles is presented, several key parameters are highlighted and novel methods suggested--emphasizing the importance of intracellular nanoparticle degradation and linking toxicity data to functional (i.e., cell-associated) nanoparticle levels, which could help to advance any progress in this highly important research topic.

The high biocompatibility and versatile nature of liposomes have made these particles keystone components in many hot-topic biomedical research areas. Liposomes can be combined with a large variety of nanomaterials, such as superparamagnetic iron oxide nanocores. Because the unique features of both the magnetizable colloid and the versatile lipid bilayer can be joined, the resulting so-called magnetoliposomes can be exploited in a great array of biotechnological and biomedical applications. In this article, we highlight the use of magnetoliposomes in immobilizing enzymes, both water-soluble and hydrophobic ones, as well as their potential in several biomedical applications, including MRI, hyperthermia cancer treatment and drug delivery. The goal of this article is not to list all known uses of magnetoliposomes but rather to present some conspicuous applications in comparison to other currently used nanoparticles.