Administration Of Iron Oxide Nanoparticles Research Articles

Study the effects of dietary administration of Iron Oxide Nanoparticles on the growth parameters of the fish Labeo rohita

Study the effects of dietary administration of Iron Oxide Nanoparticles on the growth parameters of the fish Labeo rohita

Local Administrations of Iron Oxide Nanoparticles in the Prefrontal Cortex and Caudate Putamen of Rats Do Not Compromise Working Memory and Motor Activity

Iron oxide nanoparticles (IONPs) have come into focus for their use in medical applications although possible health risks for humans, especially in terms of brain functions, have not yet been fully clarified. The present study investigates the effects of IONPs on neurobehavioural functions in rats. For this purpose, we infused dimercaptosuccinic acid-coated IONPs into the medial prefrontal cortex (mPFC) and caudate putamen (CPu). Saline (VEH) and ferric ammonium citrate (FAC) were administered as controls. One- and 4-week post-surgery mPFC-infused animals were tested for their working memory performance in the delayed alternation T-maze task and in the open field (OF) for motor activity, and CPu-infused rats were tested for their motor activity in the OF. After completion of the experiments, the brains were examined histologically and immunohistochemically. We did not observe any behavioural or structural abnormalities in the rats after administration of IONPs in the mPFC and the CPu. In contrast, administration of FAC into the CPu resulted in decreased motor activity and increased the number of microglia in the mPFC. Perls’ Prussian blue staining revealed that FAC- and IONP-treated rats had more iron-containing ramified cells than VEH-treated rats, indicating iron uptake by microglia. Our results demonstrate that local infusions of IONPs into selected brain regions have no adverse impact on locomotor behaviour and working memory.

Mammary Leukocyte-Assisted Nanoparticle Transport Enhances Targeted Milk Trace Mineral Delivery.

Nanoparticles are applied as versatile platforms for drug/gene delivery in many applications owing to their long‐retention and specific targeting properties in living bodies. However, the delivery mechanism and the beneficial effect of nanoparticle‐retention in many organisms remain largely uncertain. Here, the transport and metabolism of mineral nanoparticles in mammary gland during lactation are explored. It is shown that maternal intravenous administration of iron oxide nanoparticles (IONPs; diameter: ≈11.0 nm, surface charge: −29.1 mV, surface area: 1.05 m2 g−1) provides elevated iron delivery to mammary gland and increased iron secretion into breast milk, which is inaccessible by classical iron‐ion transport approaches such as the transferrin receptor‐mediated endocytic pathway. Mammary macrophages and neutrophils are found to play dominant roles in uptake and delivery of IONPs through an unconventional leukocyte‐assisted iron secretion pathway. This pathway bypasses the tight iron concentration regulation of liver hepcidin‐ferroportin axis and mammary epithelial cells to increase milk iron‐ion content derived from IONPs. This work provides keen insight into the metabolic pathway of nanoparticles in mammary gland while offering a new scheme of nutrient delivery for neonate metabolism regulation by using nanosized nutrients.

PB2172: IRON OXIDE NANOPARTICLES INHIBIT DIFFUSE LARGE B LYMPHOMA CELL SURVIVAL AND INVASION

Background: Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma world wide. It is a phenotypically and genetically heterogeneous disease, accounting for 30-40% of all cases. 50%-70% of patients can be cured by the R-CHOP regimen, but nearly one-third of patients develop relapsed or refractory disease. Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. But recently, more studies have revealed a hidden intrinsic therapeutic effect of ferumoxytol on tumors, but the role and mechanism in DLBCL has not been reported yet. Aims: The purpose of this study is to investigate the effect of iron oxide nanoparticles on DLBCL cells proliferation and migration by in vitro and in vivo. Methods: Different concentrations of iron oxide nanoparticles were applied to DLBCL cell lines, such as SUDHL-2 and SUDHL-4 cells, and control cells were treated with equal amounts of PBS. The proliferation, migration, apoptosis and reactive oxygen (ROS) were detected by CCK8, transwell, flow cytometry (FC) and Multifunctional Fluorescence Enzyme Marker, respectively in vitro. The engraftment, tumor growth, dissemination and survival time were observed in BALB/c nude mice and NOD-SCID mice. Results: Iron oxide nanoparticles inhibited DLBCL cells proliferation, migration and anti-apoptosis ability. The mechanism involved in the proliferation and migration of DLBCL cells by promoting the production of ROS. Furthermore, administration of iron oxide nanoparticles decreased tumor growth and dissemination of DLBCL cells, and increased survival time in the xenograft model. Summary/Conclusion: Our study demonstrates that iron oxide nanoparticles cound inhibit DLBCL cells proliferation, migration, and promote apoptosis. The supplement of iron may, therefore, be a potential target for anticancer therapy in DLBCL.

Effects of Local Administration of Iron Oxide Nanoparticles in the Prefrontal Cortex, Striatum, and Hippocampus of Rats

Iron oxide nanoparticles (IONPs) are used for diverse medical approaches, although the potential health risks, for example adverse effects on brain functions, are not fully clarified. Several in vitro studies demonstrated that the different types of brain cells are able to accumulate IONPs and reported a toxic potential for IONPs, at least for microglia. However, little information is available for the in vivo effects of direct application of IONPs into the brain over time. Therefore, we examined the cellular responses and the distribution of iron in the rat brain at different time points after local infusion of IONPs into selected brain areas. Dispersed IONPs or an equivalent amount of low molecular weight iron complex ferric ammonium citrate or vehicle were infused into the medial prefrontal cortex (mPFC), the caudate putamen (CPu), or the dorsal hippocampus (dHip). Rats were sacrificed 1 day, 1 week, or 4 weeks post-infusion and brain sections were histologically examined for treatment effects on astrocytes, microglia, and neurons. Glial scar formation was observed in the mPFC and CPu 1 week post-infusion independent of the substance and probably resulted from the infusion procedure. Compared to vehicle, IONPs did not cause any obvious additional adverse effects and no additional tissue damage, while the infusion of ferric ammonium citrate enhanced neurodegeneration in the mPFC. Results of iron staining indicate that IONPs were mainly accumulated in microglia. Our results demonstrate that local infusions of IONPs in selected brain areas do not cause any additional adverse effects or neurodegeneration compared to vehicle.

МОРФОФУНКЦІОНАЛЬНІ ЗМІНИ ВНУТРІШНІХ ОРГАНІВ ЩУРІВ ПРИ ТРИВАЛОМУ ВВЕДЕННІ В ЧЕРЕВНУ ПОРОЖНИНУ НАНОЧАСТИНОК ОКСИДУ ЗАЛІЗА (Fe2O3)

МОРФОФУНКЦІОНАЛЬНІ ЗМІНИ ВНУТРІШНІХ ОРГАНІВ ЩУРІВ ПРИ ТРИВАЛОМУ ВВЕДЕННІ В ЧЕРЕВНУ ПОРОЖНИНУ НАНОЧАСТИНОК ОКСИДУ ЗАЛІЗА (Fe2O3)

Safety assessment of chronic oral exposure to iron oxide nanoparticles

Iron oxide nanoparticles with engineered physical and biochemical properties are finding a rapidly increasing number of biomedical applications. However, a wide variety of safety concerns, especially those related to oral exposure, still need to be addressed for iron oxide nanoparticles in order to reach clinical practice. Here, we report on the effects of chronic oral exposure to low doses of γ-Fe2O3 nanoparticles in growing chickens. Animal observation, weight, and diet intake reveal no adverse signs, symptoms, or mortality. No nanoparticle accumulation was observed in liver, spleen, and duodenum, with feces as the main excretion route. Liver iron level and duodenal villi morphology reflect the bioavailability of the iron released from the partial transformation of γ-Fe2O3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe2O3 nanoparticles indicate the enhancement of a ferric over ferrous pathway supporting the role of mucins. Our findings reveal that oral administration of iron oxide nanoparticles is a safe route for drug delivery at low nanoparticle doses.

MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles

PurposeTargeting and noninvasive imaging of a specific alveolar macrophage subpopulation in the lung has revealed the importance for early and better diagnosis and therapy of chronic obstructive pulmonary disease (COPD). In this study, the in vivo effect of pulmonary administration of iron oxide nanoparticles on the polarization profile of macrophages was assessed, and a noninvasive free-breathing magnetic resonance imaging (MRI) protocol coupled with the use of biocompatible antibody-conjugated superparamagnetic iron oxide (SPIO) nanoparticles was developed to enable specific targeting and imaging of a particular macrophage subpopulation in lipopolysaccharide-induced COPD mice model.Materials and methodsEnzyme-linked immunosorbent assay, Real-time polymerase chain reaction, and flow cytometry analysis were performed to assess the biocompatibility of PEGylated dextran-coated SPIO nanoparticles. Specific biomarkers for M1 and M2 macrophages subsets were selected for conjugation with magnetic nanoparticles. MRI protocol using ultra-short echo time sequence was optimized to enable simultaneous detection of inflammation progress in the lung and detection of macrophages subsets. Flow cytometry and immunohistochemistry analysis were finally performed to confirm MRI readouts and to characterize the polarization profile of targeted macrophages.ResultsThe tested SPIO nanoparticles, under the current experimental conditions, were found to be biocompatible for lung administration in preclinical settings. Cluster of differentiation (CD)86- and CD206-conjugated magnetic nanoparticles enabled successful noninvasive detection of M1 and M2 macrophage subpopulations, respectively, and were found to co-localize with inflammatory regions induced by lipopolysaccharide challenge. No variation in the polarization profile of targeted macrophages was observed, even though a continuum switch in their polarization might occur. However, further confirmatory studies are required to conclusively establish this observation.ConclusionCoupling of magnetic iron oxide nanoparticles with a specific antibody targeted to a particular macrophage subpopulation could offer a promising strategy for an early and better diagnosis of pulmonary inflammatory diseases using noninvasive MRI.

Certain Types of Iron Oxide Nanoparticles are Not Suited to Passively Target Inflammatory Cells that Infiltrate the Brain in Response to Stroke

Intravenous administration of iron oxide nanoparticles during the acute stage of experimental stroke can produce signal intensity changes in the ischemic region. This has been attributed, albeit controversially, to the infiltration of iron-laden blood-borne macrophages. The properties of nanoparticles that render them most suitable for phagocytosis is a matter of debate, as is the most relevant timepoint for administration. Both of these questions are examined in the present study. Imaging experiments were performed in mice with 30 minutes of middle cerebral artery occlusion (MCAO). Iron oxide nanoparticles with different charges and sizes were used, and mice received 300 μmol Fe/kg intravenously: either superparamagnetic iron oxide nanoparticles (SPIOs), ultrasmall SPIOs, or very small SPIOs. The particles were administered 7 days before MCAO, at the time of reperfusion, or 72 hours after MCAO. Interestingly, there was no observable signal change in the ischemic brains that could be attributed to iron. Furthermore, no Prussian blue-positive cells were found in the brains or blood leukocytes, despite intense staining in the livers and spleens. This implies that the nanoparticles selected for this study are not phagocytosed by blood-borne leukocytes and do not enter the ischemic mouse brain.

Iron oxide nanoparticles suppressed T helper 1 cell-mediated immunity in a murine model of delayed-type hypersensitivity

BackgroundIt was recently reported that iron oxide nanoparticles attenuated antigen-specific humoral responses and T cell cytokine expression in ovalbumin-sensitized mice. It is presently unclear whether iron oxide nanoparticles influence T helper 1 cell-mediated immunity. The present study aimed to investigate the effect of iron oxide nanoparticles on delayed-type hypersensitivity (DTH), whose pathophysiology requires the participation of T helper 1 cells and macrophages.MethodsDTH was elicited by a subcutaneous challenge with ovalbumin to the footpads of mice sensitized with ovalbumin. Iron oxide nanoparticles (0.2–10 mg iron/kg) were administered intravenously 1 hour prior to ovalbumin sensitization. Local inflammatory responses were examined by footpad swelling and histological analysis. The expression of cytokines by splenocytes was measured by enzyme-linked immunosorbent assay.ResultsAdministration of iron oxide nanoparticles, in a dose-dependent fashion, significantly attenuated inflammatory reactions associated with DTH, including the footpad swelling, the infiltration of T cells and macrophages, and the expression of interferon-γ, interleukin-6, and tumor necrosis factor-α in the inflammatory site. Iron oxide nanoparticles also demonstrated a suppressive effect on ovalbumin-stimulated production of interferon-γ by splenocytes and the phagocytic activity of splenic CD11b+ cells.ConclusionThese results demonstrated that a single dose of iron oxide nanoparticles attenuated DTH reactions by suppressing the infiltration and functional activity of T helper 1 cells and macrophages in response to antigen stimulation.

Noninvasive Magnetic Resonance Imaging Detection of Cerebral Amyloid Angiopathy-Related Microvascular Alterations Using Superparamagnetic Iron Oxide Particles in APP Transgenic Mouse Models of Alzheimer's Disease: Application to Passive Aβ Immunotherapy

Cerebral amyloid angiopathy (CAA) is a common feature of Alzheimer's disease (AD). More advanced stages are accompanied by microhemorrhages and vasculitis. Peripheral blood-borne macrophages are intimately linked to cerebrovascular pathology coincident with AD. Magnetic resonance imaging (MRI) was used to noninvasively study microvascular lesions in amyloid precursor protein transgenic mouse AD models. Foci of signal attenuation were detected in cortical and thalamic brain regions of aged APP23 mice. Their strength and number was considerably enhanced by intravenous administration of iron oxide nanoparticles, which are taken up by macrophages through absorptive endocytosis, 24 h before image acquisition. The number of cortical sites displaying signal attenuation increased with age. Histology at these sites demonstrated the presence of iron-containing macrophages in the vicinity of CAA-affected blood vessels. A fraction of the sites additionally showed thickened vessel walls and vasculitis. Consistent with the visualization of CAA-associated lesions, MRI detected a much smaller number of attenuated signal sites in APP23xPS45 mice, for which a strong presenilin mutation caused a shift toward amyloid β(42), thus reducing vascular amyloid. Similar results were obtained with APP24 and APP51 mice, which develop significantly less CAA and microvascular pathology than APP23. In a longitudinal study, we noninvasively demonstrated the reinforced formation of microvascular pathology during passive amyloid β immunotherapy of APP23 mice. Histology confirmed that foci of signal attenuation reflected an increase in CAA-related lesions. Our data demonstrate that MRI has the sensitivity to noninvasively monitor the development of vascular pathology and its possible enhancement by amyloid β immunotherapy in transgenic mice modeling AD.

Challenges towards MR imaging of the peripheral inflammatory response in the subacute and chronic stages of transient focal ischemia

Intravenous administration of iron oxide nanoparticles after experimental stroke has been shown to produce focal signal intensity changes in the ischemic boundary on MRI images. These changes have been attributed to the influx of iron-laden blood-borne macrophages, although it has been suggested that this effect might not always be completely specific to inflammatory cells. The aim of the present study was to investigate this phenomenon in a subacute time frame that is more relevant to the peripheral inflammatory response. Imaging experiments (T(2) -, T(2)*- and T(1) -weighted sequences) were acquired in Wistar rats 6 days after transient middle cerebral artery occlusion (MCAO). Animals were intravenously infused with different doses of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (300, 600 or 1000 µmol Fe/kg), or saline and gadolinium, and imaged again 24 h later. Tissue was immediately processed for immunohistochemistry with the macrophage marker ED-1, in combination with Prussian blue for iron. Ischemic tissue exhibited a large increase in T(2) values, and overall contrast enhancement was apparent in the brain and surrounding muscle. In contrast with previous reports, there were no regions of focal signal intensity changes in the ischemic territory in any of the images, although a region of interest analysis revealed a trend towards iron accumulation in the ischemic hemisphere, particularly in the cortex of T(2)* images. However, histological examination revealed that, despite extensive ED-1-positive macrophage accumulation in the entire ischemic territory, none of these cells were Prussian blue positive, except in the meninges of one animal that received a high dose of USPIO nanoparticles. These results imply that the observed trend is a result of the presence of contrast agent in the blood, or meninges, and not iron-containing inflammatory cells.

2131 The dual contrast mechanism in inversion recovery with on-resonant water suppression magnetic resonance angiography (IRON-MRA) after administration of iron oxide nanoparticles

2131 The dual contrast mechanism in inversion recovery with on-resonant water suppression magnetic resonance angiography (IRON-MRA) after administration of iron oxide nanoparticles