The intensity of internalization and cytotoxicity of superparamagnetic iron oxide nanoparticles with different surface modifications in human tumor and diploid lung cells

Abstract

The human lung adenocarcinoma epithelial (A549) cells and the human embryo lung (HEL 12469) cells were used to investigate the uptake and cytotoxicity of magnetite nanoparticles (MNPs) with different chemically modified surfaces. MNPs uptake was an energy-dependent process substantially affected by the serum concentration in the culture medium. Internalized MNPs localized in vesicle-bound aggregates were observed in the cytoplasm, none in the nucleus or in mitochondria. All MNPs induced a dose-and time-dependent increase in cytotoxicity in both human lung cell lines. The cytotoxicity of MNPs increased proportionally with the particle size. Since the cytotoxicity of MNPs was nearly identical when the doses were equalized based on particle surface area, we suppose that the particle surface area rather than the surface modifications per se underlay the cytotoxicity of MNPs. In general, higher internalized amount of MNPs was found in HEL 12469 cells compared with A549 cells. Accordingly, the viability of the human embryo lung cells was reduced more substantially than that of the adenocarcinoma lung cells. The weak MNPs uptake into A549 cells might be of biomedical relevance in cases where MNPs should be used as nanocarriers for targeted drug delivery in tumor tissue derived from alveolar epithelial cells.

Effects of different doses of 2,3‐dimercaptosuccinic acid‐modified Fe2O3nanoparticles on intercalated discs in engineered cardiac tissues

“…Furthermore, DMSA‐IRONs induced the secretion of vesicles (Figure ), which was consistent with the former reports . The vesicles surrounding cell–cell connections between neighboring cardiac cells might participate in the following aspects: the modulation of cell activity, intracellular iron balance, and cell–cell communications.…”

“…51 Furthermore, DMSA-IRONs induced the secretion of vesicles (Figure 7), which was consistent with the former reports. 52 The vesicles surrounding cell-cell connections between neighboring cardiac cells might participate in the following aspects: the modulation of cell activity, intracellular iron balance, and cell-cell communications. 53,54 In regulation of cell activity, the vesicles from mitochondria were stimulated to act as the primary response to oxidative stress through delivering selected cargo to lysosomes.…”

Functionalized porous silica&maghemite core-shell nanoparticles for applications in medicine: design, synthesis, and immunotoxicity

“…On the other hand, magnetic nanoparticles induced formation of membranous ferroportin and incited secretion of ferritin, TNF-α, and IL-10 in human histiocytic lymphoma cells (U937) and human monocyte leukemia cells without any decrease of cell viability ( 27 ). A dose- and time-dependent cytotoxicity increase of oleate- or oleate/poly(ethylene glycol)/poly(lactic- co -glycolic acid)-coated magnetic particles was found in human lung adenocarcinoma epithelial (A549) and human embryo lung cells (HEL 12469) ( 28 ).…”

Mutagenic Effects of Iron Oxide Nanoparticles on Biological Cells

“…This is because the iron metabolism is well controlled whereby excess iron is efficiently removed from the body by hepcidin, which is the central regulator of iron homeostasis [ 68 ]. However, at the nanoscale, concerns arise as IONPs cause cell damage, including: disruption of cytoskeleton, apoptosis and oxidative stress in both human and mammalian cells [ 61 , 62 , 69 , 70 ]. Excess iron exposure has been found to cause elevated ROS generation through the Fenton reaction, resulting in oxidative stress that damages DNA, lipids and proteins, consequently resulting in carcinogenesis [ 71 , 72 ].…”