Assessing iron oxide nanoparticle toxicity in vitro: current status and future prospects

Abstract

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.

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…These data underscore the importance of validating the assays for each specific type of NP. Until then, researchers must assure that the measured toxicity or the lack of toxicity is indeed caused by the NP and is not merely a consequence of interference with the assay, which can be done by introducing appropriate controls 125,126 . Besides a negative (no treatment) and positive control (maximum effect), which should be included in every assay when possible, the positive control can also be tested in combination with the NP.…”

The performance of gradient alloy quantum dots in cell labeling

“…Cell differentiation assays such as performed for the C17.2 cells are also less sensitive as they take several days to perform, during which time the number of QDots per cell may have diluted. Furthermore, during the differentiation process, the cells undergo high levels of stress and the assay is accompanied by significant cell death [50]. Due to this, the cells that contain the highest number of NPs might die and the assay itself will mostly represent cells with lower numbers of NPs and may thus not be a completely accurate overview of NP toxicity.…”

Nanoparticle-based hyperthermia distinctly impacts production of ROS, expression of Ki-67, TOP2A, and TPX2, and induction of apoptosis in pancreatic cancer

“…Thus, water bath, infrared radiation, focused ultrasound, and micro-or radiowaves are some examples of heat sources placed outside the body (external heating sources). 4,5 Additionally, the progress of nanotechnology has brought a minimally-invasive approach based on the use of biocompatible 6 iron oxide magnetic nanoparticles (MNPs) as heating mediators when subjected to alternating magnetic fields (AMFs). Under these conditions, heat dissipation occurs due to magnetization reversal processes of MNP magnetic moments.…”