Toxicity Evaluations of Superparamagnetic Iron Oxide Nanoparticles: Cell “Vision” versus Physicochemical Properties of Nanoparticles

Abstract

In the last few decades, nanoparticles (NPs) have been recognized as promising candidates for starting a new revolution in science and technology due to their unusual properties, attracting the attention of physicists, chemists, biologists, and engineers. The aim of this study is to evaluate the toxicities (at both cellular and molecular levels) of three forms of superparamagnetic iron oxide nanoparticles (SPIONs) of various surface chemistries (COOH, plain, and NH(2)) through the comparison with gene expression patterns of three cell types (i.e., human heart, brain, and kidney). For this purpose, both an MTT assay and a DNA microarray analysis were applied in three human cell lines--HCM (heart), BE-2-C (brain), and 293T (kidney)--under the exposure to SPIONs-COOH, SPIONs-NH(2), and bare SPIONs. The specific gene alteration and hierarchical clustering revealed that SPIONs-COOH altered genes associated with cell proliferative responses due to their reactive oxygen species (ROS) properties. It was also found that the cell type can have quite a significant role in the definition of suitable pathways for detoxification of NPs, which has deep implications for the safe and high yield design of NPs for biomedical applications and will require serious consideration in the future.

Magnetic Nanoparticles for Precision Oncology: Theranostic Magnetic Iron Oxide Nanoparticles for Image-Guided and Targeted Cancer Therapy

“…The effect of any new formulations of IONPs should be evaluated thoroughly in experimental animals before human trials [70]. At a cellular level, induction of reactive oxygen species (ROS) after internalization of IONPs into cells has been found in vitro in various cell lines and in vivo in animal models [71]. It has been shown that internalization of SPIONs-COOH in cells increased the level of ROS that led to the alteration of the levels of expression of cell proliferative responsive genes.…”

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

“…cell culture media) surrounding the NP 31,66 . The binding of serum proteins to the NP is an important determinant in how the cells 'see' the NP and therefore influences NP uptake and toxicity [67][68][69] . The proteins forming the corona might furthermore undergo conformational changes, because of which the cell may see them as an antigen and initiate an immune response 20,30 .…”

Long term biotransformation and toxicity of dimercaptosuccinic acid-coated magnetic nanoparticles support their use in biomedical applications

“…These contradictory results are closely related to a concept known as "cell vision", refering to the contact point between nanoparticles and cells. Nanoparticles reach the plasma membrane of cells, which has a different composition depending on the cell type, and determine the "vision" that the cell has for these materials, and the effects that nanoparticles exert on the cell [17][18][19][20]. For this reason, it is necessary to analyze each nanoparticle type on an appropriate cell line.…”