Cytotoxicity Of Iron Oxide Nanoparticles Research Articles

High-Dose Exposure to Polymer-Coated Iron Oxide Nanoparticles Elicits Autophagy-Dependent Ferroptosis in Susceptible Cancer Cells.

Ferroptosis, a form of iron-dependent, lipid peroxidation-driven cell death, has been extensively investigated in recent years, and several studies have suggested that the ferroptosis-inducing properties of iron-containing nanomaterials could be harnessed for cancer treatment. Here we evaluated the potential cytotoxicity of iron oxide nanoparticles, with and without cobalt functionalization (Fe2O3 and Fe2O3@Co-PEG), using an established, ferroptosis-sensitive fibrosarcoma cell line (HT1080) and a normal fibroblast cell line (BJ). In addition, we evaluated poly (ethylene glycol) (PEG)-poly(lactic-co-glycolic acid) (PLGA)-coated iron oxide nanoparticles (Fe3O4-PEG-PLGA). Our results showed that all the nanoparticles tested were essentially non-cytotoxic at concentrations up to 100 μg/mL. However, when the cells were exposed to higher concentrations (200-400 μg/mL), cell death with features of ferroptosis was observed, and this was more pronounced for the Co-functionalized nanoparticles. Furthermore, evidence was provided that the cell death triggered by the nanoparticles was autophagy-dependent. Taken together, the exposure to high concentrations of polymer-coated iron oxide nanoparticles triggers ferroptosis in susceptible human cancer cells.

Chemical transformation and cytotoxicity of iron oxide nanoparticles (IONPs) accumulated in mitochondria

Iron oxide nanoparticles (IONPs) have been widely used as a nanoscale tool in biomedical research. However, it remains largely unknown how IONPs are transformed at a subcellular level to elicit distinct biological effects. In the present study, we prepared three different IONPs, including two IONPs targeting mitochondria (IONP-TPP) and lysosomes (IONP-APM), respectively, and a control with no specified target (IONP). By MTT assay and JC-1 staining, mitochondria-targeted IONP-TPP was found to produce significant cytotoxicity and severe mitochondrial membrane depolarization in MCF-7 cells. Furthermore, X-ray absorption spectroscopy (XAS) analysis revealed that IONP-TPP underwent remarkable edge defects and oxidation inside the cell. These findings suggest that IONPs are prone to the chemical transformation at mitochondria, and mitochondria are vulnerable to IONPs accumulation in the cell.

An Evaluation of Cytotoxicity of Iron Oxide Nanoparticles with Hydrogen Peroxide Endodontic Irrigant

Aims: The aim of this research was to determine the cytotoxic effect of different concentrations of iron oxide nanoparticles (IONPs) in combination with hydrogen peroxide ( H2O2) in vitro as a potential endodontic irrigating solution. Materials and Methods: Cytotoxicity of IONPs at concentrations (8, 4, 2, 1, 0.5, and 0.25 mg/ml) with 3% H2O2 were evaluated on cultured Human Dermal Fibroblast (HDFn) cell line. Cytotoxicity was assessed after 10 minutes of exposure using the Mosmann’s Tetrazolium Toxicity (MTT) assay. Results: Tukey’s test indicated that no significant difference in cell viability was found at lower concentrations (0.2, 0.5, 1, and 2 mg/ml). While at a concentration of 4 and 8 mg/ml, the cell viability was not significantly different from each other whereas, significantly different from previous concentrations. Conclusion: From the gained data, it can be deduced that IONPs+H2O2 had almost no cytotoxic effect on HDFn cell viability at concentrations 0.2, 0.5, 1, and 2 mg/ml, while a moderate decrease of survival has been observed at concentrations 4 and 8 mg/ml.

PHOTOCATALYTIC DEGRADATION OF METHYLENE BLUE USING IRON OXIDE NANOPARTICLES SYNTHESIZED USING ANNONA MURICATA LEAF EXTRACT

Objective: The objective of the present study is the synthesis of iron oxide nanoparticles using Annona muricata aqueous leaf extract, characterization of the synthesized nanoparticles and evaluation of the antibacterial, photocatalytic activity and cytotoxicity.
 Methods: The iron oxide nanoparticle was synthesized using Annona muricata aqueous leaf extract and the crystal structure of the iron oxide nanoparticle was determined by UV-Visible spectroscopy, Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). The in vitro cytotoxicity of iron oxide nanoparticles was evaluated using Dalton’s lymphoma ascites cells and the antibacterial assay was conducted using agar well diffusion method.
 Results: The UV-Visible spectrum of iron oxide nanoparticle showed a maximum absorption peak at 265 nm. This is the XRD pattern of iron oxide nanoparticles exhibited a distinct peak at 26.029 (2θ), accounting for crystal plane (211). SEM images revealed that the synthesized iron oxide nanoparticles were aggregated as irregular sphere shapes with rough surfaces. TEM image reveals the size of the synthesized iron oxide nanoparticles are spherical in shape with an average size of 20 nm. Green synthesized iron oxide nanoparticles using Annona muricata leaf extract effectively degraded methylene blue dye.
 Conclusion: This study showed that the synthesized iron oxide nanoparticles using Annona muricata aqueous leaf extract exhibited pronounced antibacterial, anticancer and photocatatytic activity and can be used in the textile industry for the purification of water contaminated with carcinogenic textile dyes. It can also be used as an external antiseptic in the prevention and treatment of bacterial infections.

Co-loading antioxidant N-acetylcysteine attenuates cytotoxicity of iron oxide nanoparticles in hypoxia/reoxygenation cardiomyocytes.

PurposeMyocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs.Methods and resultsAntioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe3O4 nanoparticles. Neonatal rat hypoxia/reoxygenation (H/R) cardiomyocytes were incubated with nanoparticles for 24 hrs. NAC can effectively mitigate iron-induced oxidative injury of cardiomyocytes, evidenced by reduced production of MDA, 8-iso-PGF2α, and 8-OHDG and maintained concentrations of SOD, CAT, GSH-Px, and GSH in ELISA and biochemical tests; downregulated expression of CHOP, GRP78, p62, and LC3-II proteins in Western Blot, and less cardiomyocytes apoptosis in flow cytometric analysis.ConclusionsNAC modifying could suppress the toxic effects of Fe3O4 nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.

Toxicity of iron oxide nanoparticles: Size and coating effects.

Toxicological research of novel nanomaterials is a major developmental step of their clinical approval. Since iron oxide magnetic nanoparticles have a great potential in cancer treatment and diagnostics, the investigation of their toxic properties is very topical. In this paper we synthesized bovine serum albumin-coated iron oxide nanoparticles with different sizes and their polyethylene glycol derivative. To prove high biocompatibility of obtained nanoparticles the number of in vitro toxicological tests on human fibroblasts and U251 glioblastoma cells was performed. It was shown that albumin nanoparticles' coating provides a stable and biocompatible shell and prevents cytotoxicity of magnetite core. On long exposure times (48 hours), cytotoxicity of iron oxide nanoparticles takes place due to free radical production, but this toxic effect may be neutralized by using polyethylene glycol modification.

In vitro cytotoxicity of iron oxide nanoparticles: effects of chitosan and polyvinyl alcohol as stabilizing agents

Iron oxide magnetic nanoparticles have significant potential in biomedical applications such as in diagnosis, imaging and therapeutic agent delivery. The choice of stabilizers and surface functionalization is important as it is known to strongly influence the cytotoxicity of the nanoparticles. The present study aimed at investigating the effects of surface charges on the cytotoxicity of iron oxide nanoparticles. We used a co-precipitation method to synthesize iron oxide nanoparticles which were then stabilized with either chitosan (CS) or polyvinyl alcohol (PVA) which have net positive charge and zero charge at physiological pH, respectively. The nanoparticles were characterized in terms of size, charges and chemical oxidation state. Cytotoxicity of the nanoparticles was assessed using mouse fibroblast cells and was correlated with surface charges of the nanoparticles and their aggregation.

Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings

Iron oxide nanoparticles (IONPs) have been increasingly used in biomedical applications, but the comprehensive understanding of their interactions with biological systems is relatively limited. In this study, we systematically investigated the in vitro cell uptake, cytotoxicity, in vivo distribution, clearance and toxicity of commercially available and well-characterized IONPs with different sizes and coatings. Polyethylenimine (PEI)-coated IONPs exhibited significantly higher uptake than PEGylated ones in both macrophages and cancer cells, and caused severe cytotoxicity through multiple mechanisms such as ROS production and apoptosis. 10 nm PEGylated IONPs showed higher cellular uptake than 30 nm ones, and were slightly cytotoxic only at high concentrations. Interestingly, PEGylated IONPs but not PEI-coated IONPs were able to induce autophagy, which may play a protective role against the cytotoxicity of IONPs. Biodistribution studies demonstrated that all the IONPs tended to distribute in the liver and spleen, and the biodegradation and clearance of PEGylated IONPs in these tissues were relatively slow (>2 weeks). Among them, 10 nm PEGylated IONPs achieved the highest tumor uptake. No obvious toxicity was found for PEGylated IONPs in BALB/c mice, whereas PEI-coated IONPs exhibited dose-dependent lethal toxicity. Therefore, it is crucial to consider the size and coating properties of IONPs in their applications.

Iron oxide nanoparticles and induced autophagy in human monocytes.

Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles.

Biocompatible polymeric coatings do not inherently reducethe cytotoxicity of iron oxide nanoparticles

Nanotechnology in biomedical research is an emerging and promising tool for different purposes, like high-resolution medical imaging, diagnostics, and targeted drug delivery. Although some experimental efforts focused on determination of the cytotoxicity of nanoparticles (NPs) are present, there are many controversial results. In this study, chitosan (CS)- and poly(acrylic acid) (PAA)-coated iron oxide nanoparticles (IONPs) were used to investigate the possible cytotoxicity of coated IONPs on model mammalian cell line SaOs-2 by evaluating cellular viability and membrane integrity. Increasing concentrations of IONPs increased the cytotoxic effect on SaOs-2 cells with both CS- and PAA-coated IONPs. Cell viability on day 3 was as low as 40% and 48% at 1000 ?M concentration for PAAand CS-coated IONPs, respectively, in 1% FBS-supplemented media. Cytotoxicity determined by the released lactate dehydrogenase (LDH) was as high as 163% with 1000 ?M concentration of CS-IONPs, while there was no significant change in LDH release with PAAcoated IONPs at any concentration. This study reveals that IONPs coated with a biocompatible polymer, which are usually assumed to be nontoxic, show cytotoxicity with increasing concentration and incubation time. The cytotoxicity of nanoparticles intended for biomedical purposes must be evaluated using more than one approach.

Cellular Organelle-Dependent Cytotoxicity of Iron Oxide Nanoparticles and Its Implications for Cancer Diagnosis and Treatment: A Mechanistic Investigation

Iron oxide nanoparticles (IONPs) have been widely used in the diagnosis and treatment of cancer; however, analysis of the relevant literature yields contradictory results concerning their toxicity. In this work, a bubble-generating liposomal system that can be thermally triggered to liberate its loaded IONPs instantly and precisely in defined cellular organelles is utilized to elucidate the mechanism that is responsible for the contradictory observations concerning IONP toxicity. As-prepared liposomes are internalized by test cells via endocytosis, and these internalized particles follow the endocytotic pathway from the endosomes to the lysosomes. The degradation of IONPs and the consequent release of iron ions depend strongly on the pH of the environment in the cellular organelles from which they are liberated, to which they are exposed, during their intracellular transportation. Higher IONP toxicity is associated with stronger in situ degradation with the release of more iron ions, and the consequent ge...

Characterization, Quantification, and Determination of the Toxicity of Iron Oxide Nanoparticles to the Bone Marrow Cells.

Iron oxide nanoparticles (IONPs) have been used to develop iron supplements for improving the bioavailability of iron in patients with iron deficiency, which is one of the most serious nutritional deficiencies in the world. Accurate information about the characteristics, concentration, and cytotoxicity of IONPs to the developmental and reproductive cells enables safe use of IONPs in the supplement industry. The objective of this study was to analyze the physicochemical properties and cytotoxicity of IONPs in bone marrow cells. We prepared three different types of iron samples (surface-modified iron oxide nanoparticles (SMNPs), IONPs, and iron citrate) and analyzed their physicochemical properties such as particle size distribution, zeta potential, and morphology. In addition, we examined the cytotoxicity of the IONPs in various kinds of bone marrow cells. We analyzed particle size distribution, zeta potential, iron levels, and subcellular localization of the iron samples in bone marrow cells. Our results showed that the iron samples were not cytotoxic to the bone marrow cells and did not affect the expression of cell surface markers and lipopolysaccharide (LPS)-induced the secretion of cytokines by murine bone marrow-derived dendritic cells (BMDCs). Our results may be used to investigate the interactions between nanoparticles and cells and tissues and the developmental toxicity of nanoparticles.

Investigating the cytotoxicity of iron oxide nanoparticles in in vivo and in vitro studies

In recent years, iron oxide nanorods find a lot of applications including drug delivery, cell separation, hyperthermia and magnetic resonance imaging. In this study the cytotoxicity of iron oxide nanorods was evaluated based on mouse fibroblast cell behavior and wistar rat’s liver and kidney function. At first for modification, nanorods were added to Dulbecco’s modified Eagle’s medium (DMEM) which contained a lot of sources of vitamins, amino acids, proteins in Fetal Bovine Serum (FBS). The MTT assay was employed for evaluating the toxic effects of 200 and 400μg/mL modified and non-modified iron oxide nanorods on L929 mouse fibroblast cells in a 24h period. Changes in cell granularity and size as well as cell cycle were investigated using flow cytometry. Moreover liver and kidney function test and serum iron level measurement were performed 24h after the injection of modified iron oxide nanorods via the tail peripheral vein of wistar rats. Results indicated that greater concentration of modified iron oxide nanorods had no significant effect on cell viability while greater concentration of non-modified iron oxide nanorods significantly decreased cell viability. Modified iron oxide nanorods did not have significant effects on cell cycle. The results of liver and kidney function tests did not differ significantly while a significant increase in serum iron level was observed. After H&E staining of slices, there were no changes on morphology of rat’s kidney and liver cells. This study suggests that short-time use of 200 and 400μg/mL iron oxide nanorods are probably safe. Further studies are needed for investigation of toxic effects of different concentrations, coatings, and exposure time periods of iron oxide nanorods.

The cytotoxicity of iron oxide nanoparticles with different modifications evaluated in vitro

The toxicity of magnetite nanoparticles modified with bioavailable materials such as dextran, bovine serum albumin, polyethylene glycol, and polyvinylpyrrolidone was studied in normal and cancer cells. The size distribution and magnetic properties of the modified magnetic nanoparticles were characterized by different techniques. Transmission electron microscopy showed a nearly spherical shape of the magnetite core with diameters ranging from 4 to 11 nm. Dynamic light scattering was employed to monitor the hydrodynamic size and colloidal stability of the magnetic nanoparticles: Z-average hydrodynamic diameter was between 53 and 69 nm and zeta potential in the range from −35 to −48 mV. Saturation magnetization of the modified nanoparticles was 55–64 emu/gFe3O4. Prepared biocompatible nanoparticles had no significant toxic effect on Chinese hamster lung fibroblast cell line V79, but they substantially affected mouse melanoma B16 cell line.

Cytotoxicity of iron oxide nanoparticles with different coatings on human neuronal cells

Cytotoxicity of iron oxide nanoparticles with different coatings on human neuronal cells

Synthesis, Characterization, and Cytotoxicity of Iron Oxide Nanoparticles

In order to study the response of human breast cancer cells' exposure to nanoparticle, iron oxide (α-Fe2O3) nanoparticles were synthesized by a simple low temperature combustion method using Fe(NO3)3·9H2O as raw material. X-ray diffraction studies confirmed that the resultant powders are pureα-Fe2O3. Transmission electron microscopy study revealed the spherical shape of the primary particles, and the size of the iron oxide nanoparticles is in the range of 19 nm. The magnetic hysteresis loops demonstrated that the sample exposed ferromagnetic behaviors with a relatively low coercivity. The cytotoxicity ofα-Fe2O3nanoparticle was also evaluated on human breast cancer cells to address the current deficient knowledge of cellular response to nanoparticle exposure.

In vitro evaluation of the cytotoxicity of iron oxide nanoparticles with different coatings and different sizes in A3 human T lymphocytes

The ever expanding use of engineered nanoscaled materials has brought about a commensurate growth in concern about their potential risks to human and environmental health. Toxicity of nanoparticles could vary with their physicochemical parameters. The dependence of cytotoxicity on particle size and surface coating of iron oxide nanoparticles was investigated in this in vitro study using the A3 human T lymphocyte as a model. Two different sizes (10 nm and 50 nm) and two different surface coatings (amine and carboxyl groups) of iron oxide (IO) nanoparticles were tested with fluorescein diacetate (FDA) assay and WST-1 assay. In the 1-h FDA assay with PBS, IO nanoparticles did not show size-dependent toxicity to A3 cells in terms of mass concentration; however, in terms of the number of particles per well and the total surface area, they did exhibit size-dependent toxicity. Fifty nanometer IO nanoparticles are more toxic than the 10 nm counterparts. The results of both the 24-h FDA and WST-1 assays in a complete growth medium indicate size- and surface coating-dependent toxicity to A3 cells in terms of mass concentration. IO nanoparticles of the smaller size are more toxic than those of the larger size. IO nanoparticles with the carboxyl group have a higher toxicity than those with the amine group. However, in the 24-h FDA assay, in terms of the number of particles per well and the resultant total surface area per well, the 50 nm IO nanoparticles are more toxic than those of size 10 nm. In terms of mass concentration, the number of particles per well and the total surface area, both of the 24-h assays showed the consistent results that IO nanoparticles with the carboxyl group have a higher toxicity than those with the amine group.

Cytotoxicity of iron oxide nanoparticles made from the thermal decomposition of organometallics and aqueous phase transfer with Pluronic F127

Magnetic nanoparticles are promising molecular imaging agents due to their relatively high relaxivity and the potential to modify surface functionality to tailor biodistribution. In this work we describe the synthesis of magnetic nanoparticles using organic solvents with organometallic precursors. This method results in nanoparticles that are highly crystalline and have uniform size and shape. The ability to create a monodispersion of particles of the same size and shape results in unique magnetic properties that can be useful for biomedical applications with MR imaging. Before these nanoparticles can be used in biological applications, however, means are needed to make the nanoparticles soluble in aqueous solutions and the toxicity of these nanoparticles needs to be studied. We have developed two methods to surface modify and transfer these nanoparticles to the aqueous phase using the biocompatible co-polymer, Pluronic F127. Cytotoxicity was found to be dependent on the coating procedure used. Nanoparticle effects on a cell-culture model were quantified using concurrent assaying: a lactate dehydrogenase assay to determine cytotoxicity and a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay to determine viability for a 24 h incubation period. Concurrent assaying was done to insure that nanoparticles did not interfere with the colorimetric assay results. This report demonstrates that a monodispersion of nanoparticles of uniform size and shape can be manufactured. Initial cytotoxicity testing of new molecular imaging agents needs to be carefully constructed to avoid interference and erroneous results.

The effect of grafting method on the colloidal stability and in vitro cytotoxicity of carboxymethyl dextran coated magnetic nanoparticles

The colloidal stability and cytotoxicity of iron oxide nanoparticles coated with adsorbed or covalently-bound carboxymethyl dextran (CMDx) was studied in biologically relevant buffers and in MCF-7 cell culture. Comparisons were also made with aminopropylsilane coated nanopartciles which are an intermediate step in obtaining the particles with covalently bound CMDx. Particles with covalently-bound CMDx were colloidally stable in all the buffers and in cell culture. Conversely, particles with aminopropylsilane and adsorbed CMDx precipitated under the conditions tested. Aminopropylsilane coated nanoparticles were only stable in deionized water and pH < 5. Nanoparticles with adsorbed CMDx precipitate due to desorption of CMDx in the presence of phosphates. Nanoparticles with aminopropylsilane and adsorbed CMDx were significantly more cytotoxic in the absence of magnetic field than nanoparticles with covalently-bound CMDx, which correlates with their poor colloidal stability. Both CMDx coated nanoparticles were equally effective in decreasing MCF-7 cancer cell viability by magnetic fluid hyperthermia (MFH), to levels of around 4–6%, compared to untreated samples. This study illustrates the importance of grafting method on obtaining nanoparticles suitable for biomedical applications.