The effects of iron oxide nanoparticles on antioxidant capacity and response to oxidative stress in Mozambique tilapia (Oreochromis mossambicus, Peters 1852).

Recent research has raised concern about the biocompatibility of iron oxide nanoparticles (IONPs), as they have been reported to induce oxidative stress and inflammatory responses, whilst prolonged exposure to high IONP concentrations may lead to cyto-/genotoxicity. Besides, there is concern about its environmental impact. The aim of our study was to investigate the effects of IONPs on the antioxidant defence system in freshwater fish Mozambique tilapia (Oreochromis mossambicus, Peters 1852). The fish were exposed to IONP concentration of 15 mg/L over 1, 3, 4, 15, 30, and 60 days and the findings compared to a control, unexposed group. In addition, we followed up the fish for 60 days after exposure had stopped to estimate the stability of oxidative stress induced by IONPs. Exposure affected the activity of antioxidant and marker enzymes and increased the levels of hydrogen peroxide and lipid peroxidation in the gill, liver, and brain tissues of the fish. Even after 60 days of depuration, adverse effects remained, indicating long-term nanotoxicity. Moreover, IONPs accumulated in the gill, liver, and brain tissues. Our findings underscore the potential health risks posed to non-target organisms in the environment, and it is imperative to establish appropriate guidelines for safe handling and disposal of IONPs to protect the aquatic environment.

Optimization of micelle-encapsulated extremely small sized iron oxide nanoparticles as a T1 contrast imaging agent: biodistribution and safety profile.

BACKGROUND: Iron oxide nanoparticles (IONPs) have been cleared by the Food and Drug Administration (FDA) for various clinical applications, such as tumor-targeted imaging, hyperthermia therapy, drug delivery, and live-cell tracking. However, the application of IONPs as T1 contrast agents has been restricted due to their high r2 values and r2/r1 ratios, which limit their effectiveness in T1 contrast enhancement. Notably, IONPs with diameters smaller than 5 nm, referred to as extremely small-sized IONPs (ESIONs), have demonstrated potential in overcoming these limitations. To advance the clinical application of ESIONs as T1 contrast agents, we have refined a scale-up process for micelle encapsulation aimed at improving the hydrophilization of ESIONs, and have carried out comprehensive in vivo biodistribution and preclinical toxicity assessments. RESULTS: The optimization of the scale-up micelle-encapsulation process, specifically employing Tween60 at a concentration of 10% v/v, resulted in ESIONs that were uniformly hydrophilized, with an average size of 9.35 nm and a high purification yield. Stability tests showed that these ESIONs maintained consistent size over extended storage periods and dispersed effectively in blood and serum-mimicking environments. Relaxivity measurements indicated an r1 value of 3.43 mM- 1s- 1 and a favorable r2/r1 ratio of 5.36, suggesting their potential as T1 contrast agents. Biodistribution studies revealed that the ESIONs had extended circulation times in the bloodstream and were primarily cleared via the hepatobiliary route, with negligible renal excretion. We monitored blood clearance and organ distribution using positron emission tomography and magnetic resonance imaging (MRI). Additionally, MRI signal variations in a dose-dependent manner highlighted different behaviors at varying ESIONs concentrations, implying that optimal dosages might be specific to the intended imaging application. Preclinical safety evaluations indicated that ESIONs were tolerable in rats at doses up to 25 mg/kg. CONCLUSIONS: This study effectively optimized a scale-up process for the micelle encapsulation of ESIONs, leading to the production of hydrophilic ESIONs at gram-scale levels. These optimized ESIONs showcased properties conducive to T1 contrast imaging, such as elevated r1 relaxivity and a reduced r2/r1 ratio. Biodistribution study underscored their prolonged bloodstream presence and efficient clearance through the liver and bile, without significant renal involvement. The preclinical toxicity tests affirmed the safety of the ESIONs, supporting their potential use as T1 contrast agent with versatile clinical application.

[Effects of oral exposure to iron oxide nanoparticles on reproductive system of male rats].

OBJECTIVE: To investigate the effects of oral exposure to iron oxide nanoparticles(Fe_2O_3NPs) on the reproductive system of male rats. METHODS: Forty male SD rats were randomly divided into control group and low, medium, high dose groups, 10 rats in each group, normal saline and 50, 100 and 200 mg/kg Fe_2O_3NPs suspension were given by gavage, respectively. The volume of gavage was 10 mL/kg for 28 days. The body weight was weighed every three days, and the body weight changes of rats were recorded. After intraperitoneal anesthesia with 10% chloral hydrate, the rats were sacrificed by cervical dislocation, and the testis and epididymis were collected. Weigh and calculate the testicular coefficient and epididymal coefficient, the pathological sections of rat testis were observed by hematoxylin-eosin staining, the number of epididymal sperm was counted under an optical microscope and the sperm deformity rate was calculated. The activities of acid phosphatase(ACP), alkaline phosphatase(AKP), lactate dehydrogenase(LDH) and γ-glutamyl transpeptidase(γ-GT), the activity of superoxide dismutase(SOD), and the contents of glutathione(GSH) and malondialdehyde(MDA) in rat testis homogenate were detected by kit method. RESULTS: Compared with control group, there was no significant difference in body weight, testicular coefficient and epididymal coefficient in each dose group. In the medium and high dose groups, the arrangement of spermatogenic epithelium was disordered and spermatogenic cells decreased. The number of sperm in high dose group was decreased, and the sperm deformity rate in medium and high dose groups was increased(P<0.01). The activity of ACP in medium and high dose groups increased(P<0.05), and the activity of γ-GT decreased(P<0.01). There was no significant change in the activity of AKP and LDH in testicular homogenate of rats in each group(P>0.05). The level of GSH in medium dose group was increased(P<0.05), and the content of MDA in medium and high dose groups was increased(P<0.01). There was no significant difference in SOD activity among the groups(P>0.05). CONCLUSION: Under the conditions of this experiment, Fe_2O_3NPs can cause damage to the structure of rat testicular tissue, reduce the number of sperm, increase the rate of sperm deformity, interfere with the activity of marker enzymes in testicular tissue and induce oxidative stress injury, which has a negative impact on the reproductive system of male rats.

Ultrastructural investigation of iron oxide nanoparticles accumulation in the liver of common carp (Cyprinus carpio Linnaeus, 1758).

In recent years, the intensive production of nanoparticles with a wide application has led to their transfer to the environment, including the water ecosystem. The accumulation of nanoparticles in fish, causing various pathological changes in the host, raises certain concerns. In the current study, we investigated the penetration and bioaccumulation of Fe3O4 nanoparticles, in the liver of common carp (Cyprinus carpio Linnaeus, 1758). Common carp juveniles were exposed to Fe3O4 nanoparticles at concentrations of 10 and 100 mg. After 7 days, their livers were examined by light and transmission electron microscopes. Compared to normal fish's liver, after using a small concentration (10 mg) of nanoparticles, changes were observed in erythrocytes, hepatocytes, intracellular canaliculi, and bile ducts of the liver. At a high concentration (100 mg), the intensity of changes increased significantly. The liver's capsule was damaged, and a considerable number of hepatocytes were completely destroyed. Additionally, the walls of blood vessels and biliary ductule walls was notably disturbed. It was found that the intensity of pathologies occurring in the liver, increases proportionally with higher concentrations of nanoparticles. Confirmation via electron microscopic methods revealed that Fe3O4 nanoparticles, when administered with food to common carp, enter the fish's liver through erythrocytes localized in the lumen of blood vessels. From there, they traverse through the endothelium of vessels, proceed to hepatocytes, including cytoplasmic organelles, intracellular canaliculi, biliary ductules, and eventually reach the bile ducts. Fe3O4 nanoparticles in all structural elements of fish liver was up to 20 nm. Therefore, high concentrations of nanoparticles in the environment harms the bodies of aquatic organisms, including fish. The changes identified in the liver of common carp in the present study are valuable information in assessing possible risks to other components of the aquatic ecosystem and organisms.

Lack of cytotoxic and genotoxic effects of mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium despite cellular uptake in cancerous and noncancerous lung cells.

Cytotoxic and genotoxic effects of novel mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium (Mg0.1-γ-Fe2O3(mPEG-silane)0.5) have been investigated on human adenocarcinomic alveolar basal epithelial (A549) and human normal bronchial epithelial (BEAS-2B) cells. In the studies several molecular and cellular targets addressing to cell membrane, cytoplasm organelles and nucleus components were served as toxicological endpoints. The as-synthesized nanoparticles were found to be stable in the cell culture media and were examined for different concentration and exposure times. No cytotoxicity of the tested nanoparticles was found although these nanoparticles slightly increased reactive oxygen species in both cell types studied. Mg0.1-γ-Fe2O3(mPEG-silane)0.5 nanoparticles did not produce any DNA strand breaks and oxidative DNA damages in A549 and BEAS-2B cells. Different concentration of Mg0.1-γ-Fe2O3(mPEG-silane)0.5 nanoparticles and different incubation time did not affect cell migration. The lung cancer cells' uptake of the nanoparticles was more effective than in normal lung cells. Altogether, the results evidence that mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium do not elucidate any deleterious effects on human normal and cancerous lung cells despite cellular uptake of these nanoparticles. Therefore, it seems reasonable to conclude that these novel biocompatible nanoparticles are promising candidates for further development towards medical applications.

Effects of iron oxide nanoparticles on the gene expression profiles of cerebral endotheliocytes and astrocytes.

Iron oxide nanoparticles (IONPs) are considered as the most biocompatible magnetic materials suitable for biomedical applications. Nevertheless, there are many evidences of their toxicity for living organisms and partially neurotoxicity. The central nervous system is protected from undesirable substances circulating in the bloodstream by the blood-brain barrier (BBB). And even if being small enough, some nanoparticles could be able to penetrate cell membranes in other cells but will often be delayed by the BBB cells. However, the neurotoxicity of iron oxide is described even in the cases when IONPs should not uptake to the nervous system by experimental design. The aim of this study was to investigate what molecular changes in the cells-components of BBB - endotheliocytes and underlying astrocytes - may be caused by IONPs in the blood vessels of the brain. For this, a two-layer in vitro BBB model was created, consisting of rat cerebral endothelial cells and astrocytes. It was revealed that 100 and 200 mg/L of the nanoparticles induce metabolism alteration in the cells under study. Using RNA-sequencing, the up-regulation of pro-inflammatory chemokines encoding genes and changes in the expression of genes associated with detoxification in the endotheliocytes were demonstrated under the influence of 100 mg/L IONPs.

Size, polyglycerol grafting, and net surface charge of iron oxide nanoparticles determine their interaction and toxicity in Caenorhabditis elegans.

The widespread application of engineered nanoparticles (NPs) in environmental remediation has raised public concerns about their toxicity to aquatic organisms. Although appropriate surface modification can mitigate the ecotoxicity of NPs, the lack of polymer coating to inhibit toxicity completely and the insufficient knowledge about charge effect hinder the development of safe nanomaterials. Herein, we explored the potential of polyglycerol (PG) functionalization in alleviating the environmental risks of NPs. Iron oxide NPs (ION) of 20, 100, and 200 nm sizes (IONS, IONM and IONL, respectively) were grafted with PG to afford ION-PG. We examined the interaction of ION and ION-PG with Caenorhabditis elegans (C. elegans) and found that PG suppressed non-specific interaction of ION with C. elegans to reduce their accumulation and to inhibit their translocation. Particularly, IONS-PG was completely excluded from worms of all developmental stages. By covalently introducing sulfate, carboxyl and amino groups onto IONS-PG, we further demonstrated that positively charged IONS-PG-NH3+ induced high intestinal accumulation, cuticle adhesion and distal translocation, whereas the negatively charged IONS-PG-OSO3- and IONS-PG-COO- were excreted out. Consequently, no apparent deleterious effects on brood size and life span were observed in worms treated by IONS-PG and IONS-PG bearing negatively charged groups. This study presents new surface functionalization approaches for developing ecofriendly nanomaterials.

Effects of superparamagnetic iron oxide nanoparticles (SPIONS) testicular injection on Leydig cell function and sperm production in a murine model.

In the domain of medical advancement, nanotechnology plays a pivotal role, especially in the synthesis of biocompatible materials for therapeutic use. Superparamagnetic Iron Oxide Nanoparticles (SPIONs), known for their magnetic properties and low toxicity, stand at the forefront of this innovation. This study explored the reproductive toxicological effects of Sodium Citrate-functionalized SPIONs (Cit_SPIONs) in adult male mice, an area of research that holds significant potential yet remains largely unknown. Our findings reveal that Cit_SPIONs induce notable morphological changes in interstitial cells and the seminiferous epithelium when introduced via intratesticular injection. This observation is critical in understanding the interactions of nanomaterials within reproductive biological systems. A striking feature of this study is the rapid localization of Cit_SPIONs in Leydig cells post-injection, a factor that appears to be closely linked with the observed decrease in steroidogenic activity and testosterone levels. This data suggests a possible application in developing nanostructured therapies targeting androgen-related processes. Over 56 days, these nanoparticles exhibited remarkable biological distribution in testis parenchyma, infiltrating various cells within the tubular and intertubular compartments. While the duration of spermatogenesis remained unchanged, there were many Tunel-positive germ cells, a notable reduction in daily sperm production, and reduced progressive sperm motility in the treated group. These insights not only shed light on the intricate mechanisms of Cit_SPIONs interaction with the male reproductive system but also highlight the potential of nanotechnology in developing advanced biomedical applications.

Toxicity of superparamagnetic iron oxide nanoparticles on retinoblastoma mitochondria.

PURPOSE: Retinoblastoma (RB) is one of the most important cancers in children with a higher rate of prevalence in developing countries. Despite different approaches to the treatment of RB, it seems necessary to discover a new approach to its treatment. Today, mitochondria are recognised as an important target in the treatment of cancer. Superparamagnetic iron oxide nanoparticles (SPIONs) have been studied by researchers due to their important biological effects. METHODS: In this study, the effects of SPIONs on mitochondria isolated from Y79 retinoblastoma cells were investigated. RESULTS: The results showed that SPIONs were able to increase the reactive oxygen species (ROS) level and subsequently damage the mitochondrial membrane and release cytochrome c a as one of the important pro-apoptotic proteins of RB mitochondria. Furthermore, the results indicated a decrease in cell viability and an increase in caspase-3 activity in Y79 retinoblastoma cells. CONCLUSIONS: These events can lead to the killing of cancerous mitochondria. Our results suggest that SPIONs can cause mitochondrial dysfunction and death in RB mitochondria.

Ultrasmall iron oxide nanoparticles cause significant toxicity by specifically inducing acute oxidative stress to multiple organs.

BACKGROUND: Iron oxide nanoparticles have been approved by food and drug administration for clinical application as magnetic resonance imaging (MRI) and are considered to be a biocompatible material. Large iron oxide nanoparticles are usually used as transversal (T2) contrast agents to exhibit dark contrast in MRI. In contrast, ultrasmall iron oxide nanoparticles (USPIONs) (several nanometers) showed remarkable advantage in longitudinal (T1)-weighted MRI due to the brighten effect. The study of the toxicity mainly focuses on particles with size of tens to hundreds of nanometers, while little is known about the toxicity of USPIONs. RESULTS: We fabricated Fe3O4 nanoparticles with diameters of 2.3, 4.2, and 9.3 nm and evaluated their toxicity in mice by intravenous injection. The results indicate that ultrasmall iron oxide nanoparticles with small size (2.3 and 4.2 nm) were highly toxic and were lethal at a dosage of 100 mg/kg. In contrast, no obvious toxicity was observed for iron oxide nanoparticles with size of 9.3 nm. The toxicity of small nanoparticles (2.3 and 4.2 nm) could be reduced when the total dose was split into 4 doses with each interval for 5 min. To study the toxicology, we synthesized different-sized SiO2 and gold nanoparticles. No significant toxicity was observed for ultrasmall SiO2 and gold nanoparticles in the mice. Hence, the toxicity of the ultrasmall Fe3O4 nanoparticles should be attributed to both the iron element and size. In the in vitro experiments, all the ultrasmall nanoparticles (< 5 nm) of Fe3O4, SiO2, and gold induced the generation of the reactive oxygen species (ROS) efficiently, while no obvious ROS was observed in larger nanoparticles groups. However, the ·OH was only detected in Fe3O4 group instead of SiO2 and gold groups. After intravenous injection, significantly elevated ·OH level was observed in heart, serum, and multiple organs. Among these organs, heart showed highest ·OH level due to the high distribution of ultrasmall Fe3O4 nanoparticles, leading to the acute cardiac failure and death. CONCLUSION: Ultrasmall Fe3O4 nanoparticles (2.3 and 4.2 nm) showed high toxicity in vivo due to the distinctive capability in inducing the generation of ·OH in multiple organs, especially in heart. The toxicity was related to both the iron element and size. These findings provide novel insight into the toxicology of ultrasmall Fe3O4 nanoparticles, and also highlight the need of comprehensive evaluation for their clinic application.

Hepatotoxic and Neurotoxic Potential of Iron Oxide Nanoparticles in Wistar Rats: a Biochemical and Ultrastructural Study.

Iron oxide nanoparticles (IONPs) are increasingly being employed for in vivo biomedical nanotheranostic applications. The development of novel IONPs should be accompanied by careful scrutiny of their biocompatibility. Herein, we studied the effect of administration of three formulations of IONPs, based on their starting materials along with synthesizing methods, IONPs-chloride, IONPs-lactate, and IONPs-nitrate, on biochemical and ultrastructural aspects. Different techniques were utilized to assess the effect of different starting materials on the physical, morphological, chemical, surface area, magnetic, and particle size distribution accompanied with their surface charge properties. Their nanoscale sizes were below 40 nm and demonstrated surface up to 69m2/g, and increased magnetization of 71.273 emu/g. Moreover, we investigated the effects of an oral IONP administration (100 mg/kg/day) in rat for 14 days. The liver enzymatic functions were investigated. Liver and brain tissues were analyzed for oxidative stress. Finally, a transmission electron microscope (TEM) and inductively coupled plasma optical emission spectrometer (ICP-OES) were employed to investigate the ultrastructural alterations and to estimate content of iron in the selected tissues of IONP-exposed rats. This study showed that magnetite IONPs-chloride exhibited the safest toxicological profile and thus could be regarded as a promising nanotherapeutic candidate for brain or liver disorders.

Uniform iron oxide nanoparticles reduce the required amount of polyethylenimine in the gene delivery to mesenchymal stem cells.

Cationic polyethylenimine (PEI) is regarded as the 'golden standard' of non-viral gene vectors. However, the superiority of PEI with high positive charge density also induces its major drawback of cytotoxicity, which restricts its application for an effective and safe gene delivery to stem cells. To redress this shortcoming, herein, a magnetic gene complex containing uniform iron oxide nanoparticles (UIONPs), plasmid DNA, and free PEI is prepared through electrostatic interactions for the gene delivery to bone marrow-derived mesenchymal stem cells (BM-MSCs). Results show that UIONPs dramatically promote the gene delivery to BM-MSCs using the assistance of magnetic force. In addition, decreasing the free PEI nitrogen to DNA phosphate (N/P) ratio from 10 to 6 has little adverse impact on the transgene expression levels (over 300 times than that of PEI alone at the N/P ratio of 6) and significantly reduces the cytotoxicity to BM-MSCs. Further investigations confirmed that the decrease of free PEI has little influence on the cellular uptake after applying external magnetic forces, but that the reduced positive charge density decreases the cytotoxicity. The present study demonstrates that magnetic gene delivery not only contributes to the enhanced gene expression but also helps to reduce the required amount of PEI, providing a potential strategy for an efficient and safe gene delivery to stem cells.

Quercetin attenuates neurotoxicity induced by iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) have been proposed as targeted carriers to deliver therapeutic molecules in the central nervous system (CNS). However, IONPs may damage neural tissue via free iron accumulation, protein aggregation, and oxidative stress. Neuroprotective effects of quercetin (QC) have been proven due to its antioxidant and anti-inflammatory properties. However, poor solubility and low bioavailability of QC have also led researchers to make various QC-involved nanoparticles to overcome these limitations. We wondered how high doses or prolonged treatment with quercetin conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) could improve cognitive dysfunction and promote neurogenesis without any toxicity. It can be explained that the QC inhibits protein aggregation and acts against iron overload via iron-chelating activity, iron homeostasis genes regulation, radical scavenging, and attenuation of Fenton/Haber-Weiss reaction. In this review, first, we present brain iron homeostasis, molecular mechanisms of iron overload that induced neurotoxicity, and the role of iron in dementia-associated diseases. Then by providing evidence of IONPs neurotoxicity, we discuss how QC neutralizes IONPs neurotoxicity, and finally, we make a brief comparison between QC and conventional iron chelators. In this review, we highlight that QC as supplementation and especially in conjugated form reduces iron oxide nanoparticles neurotoxicity in clinical application.

Biocompatible Superparamagnetic Europium-Doped Iron Oxide Nanoparticle Clusters as Multifunctional Nanoprobes for Multimodal In Vivo Imaging.

Magnetic nanoparticle clusters composed of primary magnetic nanoparticles can not only significantly enhance the magnetic properties of the assembly but also retain the superparamagnetic properties of the individual primary nanoparticle, which is of great significance for promoting the development of multifunctional advanced materials. Herein, water-soluble biocompatible and superparamagnetic europium-doped iron oxide nanoparticle clusters (EuIO NCs) were directly synthesized by a simple one-pot method. The obtained EuIO NCs have excellent water solubility, colloidal stability, and biocompatibility. Europium doping significantly improved the contrast enhancement effect of EuIO NCs in T1-weighted MR imaging. In addition, EuIO NCs can be functionalized by active molecules, and the rhodamine123-functionalized EuIO NCs have long circulation time and excellent fluorescence imaging performance in vivo. This study provides a simple strategy for the design and construction of a novel multifunctional magnetic nanoplatform and provides solutions for the development of multimodal imaging probes and the diagnosis of disease.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

NIR-Triggered Blasting Nanovesicles for Targeted Multimodal Image-Guided Synergistic Cancer Photothermal and Chemotherapy.

Escorting therapeutics for malignancies by nano-encapsulation to ameliorate treatment effects and mitigate side effects has been pursued in precision medicine. However, the majority of drug delivery systems suffer from uncontrollable drug release kinetics and thus lead to unsatisfactory triggered-release efficiency along with severe side effects. Herein, we developed a unique nanovesicle delivery system that shows near-infrared (NIR) light-triggered drug release behavior and minimal premature drug release. By co-encapsulation of superparamagnetic iron oxide (SPIO) nanoparticles, the ultrasound contrast agent perfluorohexane (PFH), and cisplatin in a silicate-polyaniline vesicle, we achieved the controllable release of cisplatin in a thermal-responsive manner. Specifically, vaporization of PFH triggered by the heat generated from NIR irradiation imparts high inner vesicle pressure on the nanovesicles, leading to pressure-induced nanovesicle collapse and subsequent cisplatin release. Moreover, the multimodal imaging capability can track tumor engagement of the nanovesicles and assess their therapeutic effects. Due to its precise inherent NIR-triggered drug release, our system shows excellent tumor eradication efficacy and biocompatibility in vivo, empowering it with great prospects for future clinical translation.

Effects of labeling human mesenchymal stem cells with superparamagnetic zinc-nickel ferrite nanoparticles on cellular characteristics and adipogenesis/osteogenesis differentiation.

OBJECTIVE: An attractive cell source for stem cell-based therapy are WJ-MSCs. Hence, tracking WJ-MSCs using non-invasive imaging procedures (such as MRI) and contrast agents (Zn0.5Ni0.5Fe2O4, NFNPs) are required to evaluate cell distribution, migration, and differentiation. RESULTS: Results showed that the bare and dextrin-coated NFNPs were internalized inside the WJ-MSCs and had no effect on the cell viability, proliferation, apoptosis, karyotyping, and morphology of WJ-MSCs up to 125 µg/mL. Besides, treated WJ-MSCs were differentiated into osteo/adipocyte-like cells. The expression of RUNX 2, SPP 1 (P < 0.05), and OCN (P > 0.05) genes in the WJ-MSCs treated with dextrin-coated NFNPs was higher than the untreated WJ-MSCs; and the expression of CFD, LPL, and PPAR-γ genes was reduced in WJ-MSCs treated with both NFNPs in comparison with the untreated WJ-MSCs (P > 0.05). CONCLUSION: Overall, results showed that dextrin-coated NFNPs had no adverse effect on the cellular characteristics, proliferation, and differentiation of WJ-MSCs, and suggesting their potential clinical efficacy.

Hydroxyapatite-Coated SPIONs and Their Influence on Cytokine Release.

Hydroxyapatite- or calcium phosphate-coated iron oxide nanoparticles have a high potential for use in many biomedical applications. In this study, a co-precipitation method for the synthesis of hydroxyapatite-coated nanoparticles (SPIONHAp), was used. The produced nanoparticles have been characterized by dynamic light scattering, X-ray diffraction, vibrating sample magnetometry, Fourier transform infrared spectrometry, atomic emission spectroscopy, scanning electron microscopy, transmission electron microscopy, selected area diffraction, and energy-dispersive X-ray spectroscopy. The results showed a successful synthesis of 190 nm sized particles and their stable coating, resulting in SPIONHAp. Potential cytotoxic effects of SPIONHAp on EL4, THP-1, and Jurkat cells were tested, showing only a minor effect on cell viability at the highest tested concentration (400 µg Fe/mL). The results further showed that hydroxyapatite-coated SPIONs can induce minor TNF-α and IL-6 release by murine macrophages at a concentration of 100 µg Fe/mL. To investigate if and how such particles interact with other substances that modulate the immune response, SPIONHAp-treated macrophages were incubated with LPS (lipopolysaccharides) and dexamethasone. We found that cytokine release in response to these potent pro- and anti-inflammatory agents was modulated in the presence of SPIONHAp. Knowledge of this behavior is important for the management of inflammatory processes following in vivo applications of this type of SPIONs.

Intestinal and hepatic effects of iron oxide nanoparticles.

Iron oxide nanoparticles gain increasing attention due to their broad industrial use. However, safety concerns exist since their effects on human cells are still under investigation. The presence of iron oxide nanoparticles in the food pigment E172 has been shown recently. Here, we studied four iron oxide nanoparticles, one food pigment E172 and the ionic control FeSO4 regarding dissolution in biological media, uptake and transport, and cellular effects in vitro in human intestinal Caco-2 and HepaRG hepatocarcinoma cells. The iron oxide nanoparticles passed the gastrointestinal passage without dissolution and reached the intestine in the form of particles. Minor uptake was seen into Caco-2 cells but almost no transport to the basolateral site was detected for any of the tested particles. HepaRG cells showed higher particle uptake. Caco-2 cells showed no alterations in reactive oxygen species production, apoptosis, or mitochondrial membrane potential, whereas two particles induced apoptosis in HepaRG cells, and one altered mitochondrial membrane potential at non-cytotoxic concentrations. No correlation between physicochemical particle characteristics and cellular effects was observed, thus emphasizing the need for case-by-case assessment of iron oxide nanoparticles.

Evaluation of potential immunotoxic effects of iron oxide nanoparticles (IONPs) on antioxidant capacity, immune responses and tissue bioaccumulation in common carp (Cyprinus carpio).

Nanoparticles can be toxic and put human and animals' life at risk. The present work was carried out to evaluate the possible immunosuppressive effects of water borne iron oxide nanoparticles (IONPs) and the FeCl3 on immune components of common carp (Cyprinus carpio). Fish were exposed to a series of chronic levels of 25%, 50%, and 75% of IONPs LC50 96 h concentration (referred to as control, NP1, NP2, and NP3 respectively) or FeCl3 (same concentrations as IONPs referred to as S1, S2, and S3 respectively) for 21 days. Results revealed alterations in blood parameters, where IONPs significantly decreased number of white blood cells at all concentrations. Glucose and cortisol increased in all exposed fish after 21 days, suggesting activation of the maintenance mechanism cascade against a chronic stressor. IONPs or FeCl3 significantly accumulated in liver tissue of exposed fish. Immune responses were remarkably decreased in serum and skin mucus in response to IONPs or FeCl3. These components were at lowest levels in fish exposed to the highest concentrations of IONPs and FeCl3. The findings of the present study suggested that IONPs is accumulated in fish liver and intestine, where they may exhibit immunotoxicity.