Predictive Toxicology of cobalt ferrite nanoparticles: comparative in-vitro study of different cellular models using methods of knowledge discovery from data (original) (raw)
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Toxicological Sciences, 2011
The toxicological effects of cobalt nanoparticles (Co-NPs) aggregates were examined and compared with those of cobalt ions (Co-ions) using six different cell lines representing lung, liver, kidney, intestine, and the immune system. Dose-response curves were studied in the concentration range of 0.05-1.0mM, employing 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide test, neutral red, and Alamar blue as end point assays following exposures for 48 and 72 h. Data analysis and predictive modeling of the obtained data sets were executed by employing a decision tree model (J48), where training and validation were carried out by an iterative process. It was established, as expected, that concentration is the highest rank parameter. This is because concentration parameter provides the highest information gain with respect to toxicity. The second-rank parameter emerged to be either the compound type (Co-ions or Co-NPs) or the cell model, depending on the concentration range. The third and the lowest rank in the model was exposure duration. The hierarchy of cell sensitivity toward cobalt ions was found to obey the following sequence of cell lines: A549 > MDCK > NCIH441 > Caco-2 > HepG2 > dendritic cells (DCs), with A549 being the most sensitive cell line and primary DCs were the least sensitive ones. However, a different hierarchy pattern emerged for Co-NPs: A549 5 MDCK 5 NCIH441 5 Caco-2 > DCs > HepG2. The overall findings are in line with the hypothesis that the toxic effects of aggregated cobalt NPs are mainly due to cobalt ion dissolution from the aggregated NPs.
In Vitro Evaluation of the Toxicity of Cobalt Ferrite Nanoparticles in Kidney Cell
The Turkish Journal of Pharmaceutical Sciences
Amaç: Sert manyetik kobalt ferrit nanopartiküllerinin (CoFe 2 O 4-NP) dikkate değer özellikleri ve fizikokimyasal kararlılıkları farklı endüstri ve tıp alanlarında çeşitli uygulamalarda kullanılmalarına yol açmaktadır. CoFe 2 O 4-NP'lerin bazı toksik etkilere neden olduğu bildirilmiş olsa da böbrek üzerindeki etkileri hakkında ciddi bilgi eksikliği vardır. Bu çalışmada, CoFe 2 O 4-NPs'lerinin NRK-52E böbrek hücreleri üzerine toksik etki potansiyellerinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: Partikül karakterizasyonu ve hücresel alım transmisyon elektron mikroskopu, dinamik ışık saçılma tekniği ve indüktif eşleştirilmiş plazma-kütle spektrometrisi ile gerçekleştirildi. Sonra, sitotoksisite MTT ve nötral kırmızı alım testi, genotoksisite comet tekniği ve apoptotik potansiyel propidyum iyodürlü Annexin V-FITC apoptoz tayini ile değerlendirildi. Bulgular: CoFe 2 O 4-NP'lere (39±17 nm) 100-1000 μg/mL arasında değişen konsantrasyonlarda 24 saat süre ile maruz bırakılan böbrek hücrelerinde hücre canlılığının etkilenmediği, ancak ≤100 μg/mL'de önemli ölçüde DNA hasarı meydana geldiği gözlenmiştir. Maruz kalan hücrelerde apoptotik veya nekrotik etki gözlenmedi. Sonuç: Elde edilen sonuçlara göre, CoFe 2 O 4-NP'ler çeşitli uygulamalarda güvenli kullanımı vaat etmektedir. Bununla birlikte, etki mekanizmalarının tam olarak anlaşılabilmesi için in vivo çalışmalara ihtiyaç vardır. Anahtar kelimeler: DNA hasarı, hücre ölümü, apoptoz, kobalt ferrit nanopartikülü Objectives: The remarkable properties of hard magnetic cobalt ferrite nanoparticles (CoFe 2 O 4-NPs) and their physicochemical stability lead to various applications in different industrial and medical fields. Although CoFe 2 O 4-NPs have been reported to cause toxic effects, there is a serious lack of information concerning their effects on the kidneys. In this study, it was aimed to investigate the toxic effects of CoFe 2 O 4-NPs on NRK-52E kidney cells. Materials and Methods: The particle characterisation and cellular uptake were determined using transmission electron microscopy, dynamic light scattering and inductively coupled plasma-mass spectrometry. Then, the cytotoxicity was evaluated by MTT and neutral red uptake assays, the genotoxicity by comet assay, and the apoptotic potentials by Annexin V-FITC apoptosis detection assay with propidium iodide. Results: After 24 h exposure to CoFe 2 O 4-NPs (39±17 nm), it was observed they did not affect the cell viability at concentration ranging from 100 to 1000 μg/mL, but significantly induced DNA damage at concentration ≤100 μg/mL. No apoptotic or necrotic effect was observed in the exposed cells. Conclusion: According to the results obtained, CoFe 2 O 4-NPs are promising for safe use in various applications. However, further in vivo studies are needed to fully understand their mechanisms of action.
Biological Trace Element Research
Cobalt ferrite nanoparticles (CFN) are employed in data storage, imaging, medication administration, and catalysis due to their superparamagnetic characteristics. The widespread use of CFN led to significantly increased exposure to people and the environment to these nanoparticles. Until now, there is not any published paper describing the adverse effect of repeated oral intake of this nanoformulation on rats’ lungs. So, the current research aims to elucidate the pulmonary toxicity prompted by different concentrations of CFN in rats as well as to explore the mechanistic way of such toxicity. We used 28 rats that were divided equally into 4 groups. The control group received normal saline, and the experimental groups received CFN at dosage levels 0.05, 0.5, and 5 mg/kg bwt. Our findings revealed that CFN enhanced dose-dependent oxidative stress manifested by raising in the MDA levels and declining in the GSH content. The histopathological examination revealed interstitial pulmonary i...
Nanotoxicology, 2012
Different in vitro assays are successfully used to determine the relative cytotoxicity of a broad range of compounds. Nevertheless, different research groups have pointed out the difficulty in using the same tests to assess the toxicity of nanoparticles (NPs). In this study, we evaluated the possible use of a microphysiometer, Bionas 2500 analyzing system Bionas GmbH Ò , to detect in real time changes in cell metabolisms linked to NPs exposure. We focused our work on response changes of fibroblast cultures linked to exposure by cobalt ferrite NPs and compared the results to conventional in vitro assays. The measurements with the microphysiometer showed a cobalt ferrite cytotoxic effect, confirmed by the Colony Forming Efficiency assay. In conclusion, this work demonstrated that the measurement of metabolic parameters with a microphysiometer is a promising method to assess the toxicity of NPs and offers the advantage to follow on-line the cell metabolic changes.
Medicina, 2014
m e d i c i n a 5 0 ( 2 0 1 4 ) 2 3 7 -2 4 4 Cytotoxicity Pancreatic cancer Ovarian cancer Cancer stem-like cells a b s t r a c t Background and objective: Superparamagnetic iron oxide nanoparticles (SPIONs) emerge as a promising tool for early cancer diagnostics and targeted therapy. However, both toxicity and biological activity of SPIONs should be evaluated in detail. The aim of this study was to synthesize superparamagnetic cobalt ferrite nanoparticles (Co-SPIONs), and to investigate their uptake, toxicity and effects on cancer stem-like properties in human pancreatic cancer cell line MiaPaCa2 and human ovarian cancer cell line A2780. Materials and methods: Co-SPIONs were produced by Massart's co-precipitation method. The cells were treated with Co-SPIONs at three different concentrations (0.095, 0.48, and 0.95 mg/ mL) for 24 and 48 h. Cell viability and proliferation were analyzed after treatment. The stemlike properties of cells were assessed by investigating the cell clonogenicity and expression of cancer stem cell-associated markers, including CD24/ESA in A2780 cell line and CD44/ ALDH1 in MiaPaCa2 cell line. Magnetically activated cell sorting was used for the separation of magnetically labeled and unlabeled cells.
Cellular distribution and degradation of cobalt ferrite nanoparticles in Balb/3T3 mouse fibroblasts
Toxicology letters, 2011
The effect of the concentration of cobalt ferrite (CoFe(2)O(4)) nanoparticles (NPs) on their intracellular location and distribution has been explored by synchrotron radiation X-ray and fluorescence microscopy (SR-XRF) monitoring the evolution of NPs elemental composition as well. In cells exposed to low concentrations of CoFe(2)O(4) NPs, the NPs preferentially segregate in the perinuclear region preserving their initial chemical content. At concentrations exceeding 500 μM the XRF spectra indicate the presence of Co and Fe also in the nuclear region, accompanied by sensible changes in the cellular morphology. The increase of the Co/Fe ratio measured in the nuclear compartment indicates that above certain concentrations the CoFe(2)O(4) NPs intracellular distribution could be accompanied by biodegradation resulting in Co accumulation in the nucleus.
SN Applied Sciences
In this study, we report the synthesis and characterization of NiFe2O4 and CoFe2O4 nanoparticles (NPs) which are widely used in the biomedical area. There is still limited knowledge how the properties of these materials are influenced by different chemical routes. In this work, we investigated the effect of heat treatment over cytotoxicity of cobalt and niquel ferrites NPs synthesized by sol-gel method. Then the samples were studied using transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), Fourier Transform Infrared Spectroscopy Analysis (FTIR), and X-ray fluorescence (XRF). The average crystallite sizes of the particles were found to be in the range of 20–35 nm. The hemocompatibility (erythrocytes and leukocytes) was checked. Cytotoxicity results were similar to those of the control test sample, therefore suggesting hemocompatibility of the tested materials.
Cobalt Ferrite Nanoparticles for Tumor Therapy: Effective Heating versus Possible Toxicity
Nanomaterials, 2021
Magnetic nanoparticles (MNPs) are widely considered for cancer treatment, in particular for magnetic hyperthermia (MHT). Thereby, MNPs are still being optimized for lowest possible toxicity on organisms while the magnetic properties are matched for best heating capabilities. In this study, the biocompatibility of 12 nm cobalt ferrite MNPs, functionalized with citrate ions, in different dosages on mice and rats of both sexes was investigated for 30 days after intraperitoneal injection. The animals’ weight, behavior, and blood cells changes, as well as blood biochemical parameters are correlated to histological examination of organs revealing that cobalt ferrite MNPs do not have toxic effects at concentrations close to those used previously for efficient MHT. Moreover, these MNPs demonstrated high specific loss power (SLP) of about 400 W g−1. Importantly the MNPs retained their magnetic properties inside tumor tissue after intratumoral administration for several MHT cycles within thre...
Toxicity of cobalt oxide nanoparticles to normal cells; an in vitro and in vivo study
Chemico-Biological Interactions, 2015
The aim of this study was to find out the intracellular signaling transduction pathways involved in cobalt 30 oxide nanoparticles (CoO NPs) mediated oxidative stress in vitro and in vivo system. Cobalt oxide nano-31 particles released excess Co ++ ions which could activated the NADPH oxidase and helps in generating the 32 reactive oxygen species (ROS). Our results showed that CoO NPs elicited a significant (p < 0.05) amount of 33 ROS in lymphocytes. In vitro pretreatment with N-acetylene cystine had a protective role on lymphocytes 34 death induced by CoO NPs. In vitro and in vivo results showed the elevated level of TNF-a after CoO NPs 35 treatment. This TNF-a phosphorylated the p38 mitogen-activated protein kinase followed by activation 36 of caspase 8 and caspase 3 which could induce cell death. This study showed that CoO NPs induced 37 oxidative stress and activated the signaling pathway of TNF-a-caspase-8-p38-caspase-3 to primary 38 immune cells. This study suggested that bare CoO NPs are a toxic for primary human immune cells that 39 deals directly with human health. Surface modification or surface functionalization may open the gate-40 way for further use of CoO NPs in different industrial use or in biomedical sciences.
The broad spectrum applications of CoFe2O4 NPs have attracted much interest in medicine, environment and industry, resulting in exceedingly higher exposures to humans and environmental systems in succeeding days. Their health effects and potential biological impacts need to be determined for risk assessment. Zebrafish (Danio rerio) embryos were exposed to environmentally relevant doses of nanoCoFe2O4 (mean diameter of 40 nm) with a concentration range of 10–500 M for 96 h. Acute toxic end points were evaluated by survival rate, malformation, hatching delay, heart dysfunction and tail flexure of larvae. Dose and time dependent developmental toxicity with severe cardiac edema, down regulation of metabolism, hatching delay and tail/spinal cord flexure and apoptosis was observed. The biochemical changes were evaluated by ROS, Catalase (CAT), Lipid peroxidation (LPO), Acid phophatase (AP) and Glutatione s- transferase (GST). An Agglomeration of NPs and dissolution of ions induces severe mechanical damage to membranes and oxidative stress. Severe apoptosis of cells in the head, heart and tail region with inhibition of catalase confirms ROS induced acute toxicity with increasing concentration. Increased activity of GST and AP at lower concentrations of CoFe2O4 NPs demonstrates the severe oxidative stress. Circular dichroism (CD) spectra indicated the weak interactions of NPs with BSA and slight changes in -helix structure. In addition, CoFe2O4 NPs at lower concentrations do not show any considerable interference with assay components and analytical instruments. The results are possible elucidation of pathways of toxicity induced by these particles, as well as contributing in defining the protocols for risk assessment of these nanoparticles.