ROS-induced toxicity: exposure of 3T3, RAW264.7, and MCF7 cells to superparamagnetic iron oxide nanoparticles results in cell death by mitochondria-dependent apoptosis
Journal
Journal of Nanoparticle Research
Journal Volume
17
Journal Issue
2
Pages
-
Date Issued
2015
Author(s)
Abstract
Superparamagnetic nanoparticles (Fe3O4, SPIO) have been used as magnetic resonance imaging enhancers for years. However, bio-safety issues concerning nanoparticles remain largely unexplored. Of particular concern is the possible cellular impact of nanoparticles during SPIO uptake and subsequent oxidative stress. SPIO causes cell death by apoptosis via a little understood mitochondrial pathway. To more closely examine this process, three kinds of cells—3T3, RAW264.7, and MCF7—were treated with SPIO coated with polyethylene glycol (SPIO-PEG) and monitored by transmission electron microscopy (TEM), using cytotoxicity evaluation, mitochondrial activity, reactive oxygen species (ROS) generation, and Annexin V assay. TEM revealed that SPIO-PEG nanoparticles surrounded the cellular endosome membrane, creating a bulge in the endosome. Compared to 3T3 cells, greater numbers of SPIO-PEG nanoparticles infiltrated the mitochondria of RAW264.7 and MCF7 cells. SPIO-PEG residency is associated with boosted ROS, with elevated levels of mitochondrial activity, and advancement of cell apoptosis. Furthermore, correlation analysis showed that a polynomial model demonstrates a better fit than a linear model in MCF7, implying that cytotoxicity may have alternative impacts on cell death at different concentrations. Thus, we believe that MCF7 cell death results from the apoptosis pathway triggered by mitochondria, and we find lower cytotoxicity in 3T3. We propose that optimal levels of SPIO-PEG nanoparticles lead to increased levels of ROS and a resulting oxidative stress environment which will kill only cancer cells while sparing normal cells. This finding has great potential for use in cancer therapies in the future. ? 2015, Springer Science+Business Media Dordrecht.
SDGs
Other Subjects
Cell death; Cytotoxicity; Diseases; High resolution transmission electron microscopy; Iron oxides; Magnetic resonance imaging; Magnetite; Mitochondria; Superparamagnetism; Cancer; Correlation analysis; Environmental and health effects; Mitochondrial activity; Mitochondrial pathways; Superparamagnetic iron oxide nanoparticles; Superparamagnetic nanoparticles; Superparamagnetics; Magnetic nanoparticles; lipocortin 5; macrogol; nanocoating; reactive oxygen metabolite; superparamagnetic iron oxide nanoparticle; 3T3 cell line; animal cell; apoptosis; Article; cell count; cell death; cell killing; cell viability; controlled study; correlation analysis; crystal structure; cytotoxicity; endosome; human; human cell; hydrodynamics; lysosome; macrophage; MCF 7 cell line; mitochondrion; mouse; nonhuman; oxidative stress; particle size; priority journal; RAW264.7 cell line; transmission electron microscopy
Type
journal article