Effect Of Superparamagnetic Iron Oxide Nanoparticles Research Articles

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.

The antidiabetic effect of superparamagnetic iron oxidenanoparticles highlights the role of WNT/AMPK/mTOR/FOXO1/mitochondrialDNA in muscle and kidney.

Aim: To explore the antidiabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs)-PEG-550 and its related metabolic pathways in muscles and kidney. Materials & methods: Diabetes was induced in 5-day neonatal rats; after confirming diabetes, treatment with SPIONs-PEG-550 started at different doses for 4weeks. Routine analysis of glucose, insulin, adipocytokines, urea and creatinine was performed. The expression of several genes involved in metabolic pathways and the corresponding protein levels were examined. Results & conclusion: SPIONs-PEG-550 normalized the disturbed glucose homeostasis, reversed insulin resistance, adjusted the serum level of adipocytokines, andimproved several disturbed downstream effectors of the insulin signaling and WNT pathway in both tissues. Histological examination of the muscle and pancreas has shown almost normal functional characteristics without remarkable adverse effects on the kidney.

Superparamagnetic Iron Oxide Nanoparticles and Static Magnetic Field Regulate Neural Stem Cell Proliferation.

Neural stem cells (NSCs) transplantation is a promising approach for the treatment of various neurodegenerative diseases. Superparamagnetic iron oxide nanoparticles (SPIOs) are reported to modulate stem cell behaviors and are used for medical imaging. However, the detailed effects of SPIOs under the presence of static magnetic field (SMF) on NSCs are not well elucidated. In this study, it was found that SPIOs could enter the cells within 24 h, while they were mainly distributed in the lysosomes. SPIO exhibited good adhesion and excellent biocompatibility at concentrations below 500 μg/ml. In addition, SPIOs were able to promote NSC proliferation in the absence of SMF. In contrast, the high intensity of SMF (145 ± 10 mT) inhibited the expansion ability of NSCs. Our results demonstrate that SPIOs with SMF could promote NSC proliferation, which could have profound significance for tissue engineering and regenerative medicine for SPIO applications.

Mechanisms for cellular uptake of nanosized clinical MRI contrast agents

Engineered Nanomaterials (NMs), such as Superparamagnetic Iron Oxide Nanoparticles (SPIONs), offer significant benefits in a wide range of applications, including cancer diagnostic and therapeutic strategies. However, the use of NMs in biomedicine raises safety concerns due to lack of knowledge on possible biological interactions and effects. The initial basis for using SPIONs as biomedical MRI contrast enhancement agents was the idea that they are selectively taken up by macrophage cells, and not by the surrounding cancer cells. To investigate this claim, we analyzed the uptake of SPIONs into well-established cancer cell models and benchmarked this against a common macrophage cell model. In combination with fluorescent labeling of compartments and siRNA silencing of various proteins involved in common endocytic pathways, the mechanisms of internalization of SPIONs in these cell types has been ascertained utilizing reflectance confocal microscopy. Caveolar mediated endocytosis and macropinocytosis are both implicated in SPION uptake into cancer cells, whereas in macrophage cells, a clathrin-dependant route appears to predominate. Colocalization studies confirmed the eventual fate of SPIONs as accumulation in the degradative lysosomes. Dissolution of the SPIONs within the lysosomal environment has also been determined, allowing a fuller understanding of the cellular interactions, uptake, trafficking and effects of SPIONs within a variety of cancer cells and macrophages. Overall, the behavior of SPIONS in non-phagocytotic cell lines is broadly similar to that in the specialist macrophage cells, although some differences in the uptake patterns are apparent.

MRI-Tracking of Dental Pulp Stem Cells In Vitro and In Vivo Using Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles.

The aim of this study was to track dental pulp stem cells (DPSCs) labeled with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) using magnetic resonance imaging (MRI). Dental pulp was isolated from male Sprague Dawley rats and cultured in Dulbecco’s modified Eagle’s medium F12 (DMEM-F12) and 10% fetal bovine serum. Effects of SPIONs on morphology, viability, apoptosis, stemness, and osteogenic and adipogenic differentiation of DPSCs were assessed. Prussian blue staining and MRI were conducted to determine in vitro efficiency of SPIONs uptake by the cells. Both non-labeled and labeled DPSCs were adherent to culture plates and showed spindle-shape morphologies, respectively. They were positive for osteogenic and adipogenic induction and expression of cluster of differentiation (CD) 73 and CD90 biomarkers, but negative for expression of CD34 and CD45 biomarkers. The SPIONs were non-toxic and did not induce apoptosis in doses less than 25 mg/mL. Internalization of the SPIONs within the DPSCs was confirmed by Prussian blue staining and MRI. Our findings revealed that the MRI-based method could successfully monitor DPSCs labeled with dextran-coated SPIONs without any significant effect on osteogenic and adipogenic differentiation, viability, and stemness of DPSCs. We provided the in vitro evidence supporting the feasibility of an MRI-based method to monitor DPSCs labeled with SPIONs without any significant reduction in viability, proliferation, and differentiation properties of labeled cells, showing that internalization of SPIONs within DPSCs were not toxic at doses less than 25 mg/mL. In general, the SPION labeling does not seem to impair cell survival or differentiation. SPIONs are biocompatible, easily available, and cost effective, opening a new avenue in stem cell labeling in regenerative medicine.

Superparamagnetic iron oxide nanoparticles (SPIONs) modulate hERG ion channel activity

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in various biomedical applications, such as diagnostic agents in magnetic resonance imaging (MRI), for drug delivery vehicles and in hyperthermia treatment of tumors. Although the potential benefits of SPIONs are considerable, there is a distinct need to identify any potential cellular damage associated with their use. Since human ether à go-go-related gene (hERG) channel, a protein involved in the repolarization phase of cardiac action potential, is considered one of the main targets in the drug discovery process, we decided to evaluate the effects of SPIONs on hERG channel activity and to determine whether the oxidation state, the dimensions and the coating of nanoparticles (NPs) can influence the interaction with hERG channel. Using patch clamp recordings, we found that SPIONs inhibit hERG current and this effect depends on the coating of NPs. In particular, SPIONs with covalent coating aminopropylphosphonic acid (APPA) have a milder effect on hERG activity. We observed that the time-course of hERG channel modulation by SPIONs is biphasic, with a transient increase (∼20% of the amplitude) occurring within the first 1–3 min of perfusion of NPs, followed by a slower inhibition. Moreover, in the presence of SPIONs, deactivation kinetics accelerated and the activation and inactivation I–V curves were right-shifted, similarly to the effect described for the binding of other divalent metal ions (e.g. Cd2+ and Zn2+). Finally, our data show that a bigger size and the complete oxidation of SPIONs can significantly decrease hERG channel inhibition. Taken together, these results support the view that Fe2+ ions released from magnetite NPs may represent a cardiac risk factor, since they alter hERG gating and these alterations could compromise the cardiac action potential.

Superparamagnetic iron oxide (SPIO) nanoparticles labeled endothelial progenitor cells (EPCs) administration inhibited heterotopic ossification in rats

Heterotopic ossification (HO) is a painful disease characterized by unwanted bone ectopic formation outside of the skeleton after injury. SPIO nanoparticles therapy has been widely used in diverse orthopedic diseases. However, the effect of SPIO nanoparticles on heterotopic ossification remains unknown. Here, we prepared the SPIO nanoparticles carrying mothers against decapentaplegic homolog 7 (SMAD7) and evaluated their mechanism function to HO in a rat model. The results revealed that SPIO nanoparticles containing SMAD7 treatment lead to a decrease in epithelial-mesenchymal transition (EMT) relevant protein expression in vitro. Moreover, SPIO nanoparticles labeled EPCs transplantation effectively prevented heterotopic ossification and inhibited endothelial-mesenchymal transition (EndMT) in HO rats. In addition, SPIO nanoparticles labeled EPCs transplantation suppressed osteogenic and adipogenic differentiation of embryonic fibroblasts (EFs) in HO rats. Our results demonstrated that administration of SPIO nanoparticles labeled EPCs could inhibit heterotopic ossification in rats, which might be a potential therapy method for a medical intervention to treat HO in clinic.

Effect of superparamagnetic nanoparticles coated with various electric charges on α-synuclein and β-amyloid proteins fibrillation process.

BackgroundMost of nanoparticles are nontoxic and have high absorption capability. Therefore, nanoparticles binding can effectively restrain fibrillation of β-amyloid and α-synuclein proteins and eventually prevent the toxicity of pathogenesis peptide of Alzheimer. Super paramagnetic iron oxide nanoparticles (SPIONs) contain iron oxide core which can be connected to a special part through magnetic coating.Materials and methodsIn this study, the effect of SPIONs with different charges was simultaneously examined on the fibrillation of both β-amyloid and α-synuclein proteins by applying Thioflavin-T assay.ResultsAccording to the results of the investigation on amyloid-fibrillation mechanism in both β-amyloids and α-synucleins, it was revealed that negatively-charged nanoparticles encoded to –COOH by dextran-coating were able to have a considerable absorption decrease from 17,000–12,000 after 320 minutes delay to lag phase and decrease in binding level of thioflavin-T particles to β-sheets.ConclusionThe different concentrations of these nanoparticles and special coating of each particle had an effect on the kinetics of β-amyloid and α-synuclein fibrillations.

Synthesis and characterization of polyglycerol coated superparamagnetic iron oxide nanoparticles and cytotoxicity evaluation on normal human cell lines

Superparamagnetic iron oxide nanoparticles (SPIONs) are considered as interesting nano-carriers for cancer detection and treatment. As promising reagents for biomedical applications they need surface modifications and polyglycerol has shown suitable characteristics as a coating agent in this regard. Synthesis and characterization of SPIONs and polyglycerol coated SPIONs (PG-SPIONs) as well as evaluation of cytotoxic effects on normal human cell lines (HEK293 and MCF10A) was the aim of present study. The effect of SPIONs and PG-SPIONs on these cell lines was evaluated by measuring the cell viability, apoptosis, expression of apoptosis-associated proteins and caspase-3 activity. Characteristics of nanoparticles were determined by TEM, FTIR, VSM and XRD. Mean size of SPIONs and PG-SPIONs were found to be 5.4 ± 0.75 nm and 17.9 ± 2.85 nm, respectively. XRD result demonstrates that the nanoparticles are Fe3O4 with highly crystalline particles and their surface modification by Polyglycerol (PG) and superparamagnetic behavior was confirmed by FTIR and VSM. The surface coating significantly increased cell viability, attenuated apoptosis, promoted expression of Bax and P53 and reduced Bcl2 protein expression and caspase-3 activity. In conclusion, these results indicates that surface coating of SPIONs with PG can decrease SPIONs-induced cell injury in normal human cells, suggesting PG-SPIONs as safe nanocarriers for application in medicine.

Effects of superparamagnetic iron oxide nanoparticles on the longitudinal and transverse relaxation of hyperpolarized xenon gas

SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) are often used in magnetic resonance imaging experiments to enhance Magnetic Resonance (MR) sensitivity and specificity. While the effect of SPIONs on the longitudinal and transverse relaxation time of 1H spins has been well characterized, their effect on highly diffusive spins, like those of hyperpolarized gases, has not. For spins diffusing in linear magnetic field gradients, the behavior of the magnetization is characterized by the relative size of three length scales: the diffusion length, the structural length, and the dephasing length. However, for spins diffusing in non-linear gradients, such as those generated by iron oxide nanoparticles, that is no longer the case, particularly if the diffusing spins experience the non-linearity of the gradient. To this end, 3D Monte Carlo simulations are used to simulate the signal decay and the resulting image contrast of hyperpolarized xenon gas near SPIONs. These simulations reveal that signal loss near SPIONs is dominated by transverse relaxation, with little contribution from T1 relaxation, while simulated image contrast and experiments show that diffusion provides no appreciable sensitivity enhancement to SPIONs.

Study of antimicrobial effects of several antibiotics and iron oxide nanoparticles on biofilm producing pseudomonas aeruginosa

Objective(s): Pseudomonas aeruginosa is a nosocomial pathogen resistant to most antimicrobial treatments. Furthermore, it persists in adverse environments thereby forming biofilms on various surfaces. Researchers have therefore focused on antibiofilm strategies using nanoparticles due to their unique physicochemical properties. Superparamagnetic iron oxide nanoparticles (SIONPs) have recently shown to possess antimicrobial and anti-biofilm characteristics. In this study, the effects of SIONPs and some antibiotics were tested against strong biofilmproducing P. aeruginosa isolates.Materials and Methods: 60 isolates of P.aeruginosa were screened for biofilm formation on microtiter plates using 0.1%w/v crystal violet (CV) staining. Twenty isolates producing strong biofilms were selected for further study on the effects of antimicrobial agents. Microdilution method was used to assay twenty isolates susceptible to antibiotics. The effects of antibiotics and SIONPs on biofilm formation were determined by the microdilution method and 0.1% CV staining. The checkerboard dilution technique was used to determine the combined effects of SIONPs and imipenem. Results: In twenty isolates, the rate of resistance to ciprofloxacin, levofloxacin, amikacin, azithromycin was 65, 75, 45 and 95% respectively. SIONPs at 30 µg/ml reduced biofilm biomass in 11 isolates; however it stimulated biofilm formation in 9 isolates. The effects of SIONPs in combination with imipenem in the 10 isolates were different exhibiting synergistic or antagonistic relationships.Conclusion: P. aeruginosa has increasingly developed resistance to many antimicrobial agents but the resistance to nanoparticles is less frequently been reported. However, iron oxide nanoparticles could enhance biofilm production in isolate- dependent manner because they may possibly utilize this nanoparticle as an iron source, an important element in biofilm production. The exact mechanism of these effects however, remains to be elucidated.

Lipoamino Acid Coated Superparamagnetic Iron Oxide Nanoparticles Concentration and Time Dependently Enhanced Growth of Human Hepatocarcinoma Cell Line (Hep‐G2)

Superparamagnetic iron oxide nanoparticles (SPION) have been widely used in medicine for magnetic resonance imaging, hyperthermia, and drug delivery applications. The effect of SPION on animal cells has been a controversial issue on which there are many contradictions. This study focused on preparation of SPION with novel biocompatible coatings, their characterization, and cytotoxicity evaluation. An amino acid (glycine) and two novel lipo‐amino acids (2 amino‐hexanoic acid and 2 amino‐hexadecanoic acid) coated magnetic nanoparticles were characterized by various physicochemical means such as X‐ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), differential scanning calorimetry (DSC), and infrared spectroscopy (FT‐IR). The cytotoxicity profile of the synthesized nanoparticles on Hep‐G2 cells as measured by MTT assay showed the nanoparticles are nontoxic and the cell growth is promoted by SPION. Moreover, lipoamino acid coating SPION appear more beneficial than the other ones. By increasing concentration of SPION, growth enhancing impact will attenuate and toxicity will appear. Although the aggregation of SPION can affect the results, the gradual delivery of ferric/ferrous ions into cells is the main cause of this growth promotion effect. Conclusively, this study shows that lipoamino acid coating SPION can be used for various biomedical purposes.

Stem cell tracking using iron oxide nanoparticles.

Superparamagnetic iron oxide nanoparticles (SPIONs) are an exciting advancement in the field of nanotechnology. They expand the possibilities of noninvasive analysis and have many useful properties, making them potential candidates for numerous novel applications. Notably, they have been shown that they can be tracked by magnetic resonance imaging (MRI) and are capable of conjugation with various cell types, including stem cells. In-depth research has been undertaken to establish these benefits, so that a deeper level of understanding of stem cell migratory pathways and differentiation, tumor migration, and improved drug delivery can be achieved. Stem cells have the ability to treat and cure many debilitating diseases with limited side effects, but a main problem that arises is in the noninvasive tracking and analysis of these stem cells. Recently, researchers have acknowledged the use of SPIONs for this purpose and have set out to establish suitable protocols for coating and attachment, so as to bring MRI tracking of SPION-labeled stem cells into common practice. This review paper explains the manner in which SPIONs are produced, conjugated, and tracked using MRI, as well as a discussion on their limitations. A concise summary of recently researched magnetic particle coatings is provided, and the effects of SPIONs on stem cells are evaluated, while animal and human studies investigating the role of SPIONs in stem cell tracking will be explored.

Effects of Magnetite Nanoparticles on Soybean Chlorophyll

Nanoparticles (NPs) have emerged as one of the most innovative and promising application in agriculture. Since plants are recognized as essential component of all ecosystems, the effects of NPs on plants may pave a new insight to the ecosystems. Here, uptake and translocation of superparamagnetic iron oxide NPs (SPIONs), with various surface charges, on soybean has been probed; in addition, the effects of SPIONs on variations of chlorophyll, in hydroponic condition, together with their ability for reduction of iron deficiency chlorosis were explored. We find that SPIONs, which were entered and translocated in the soybean, increased chlorophyll levels, with no trace of toxicity. Furthermore, it was found that physicochemical characteristics of the SPIONs had a crucial role on the enhancement of chlorophyll content in subapical leaves of soybean. The equivalent ratio of chlorophyll a to b, in all treatments with conventional growth medium iron chelate and SPIONs (as iron source), indicated no significant difference on the photosynthesis efficiency. Finally, it was observed that the effect of SPIONs on the soybean chlorophyll content may have influence on both biochemical and enzymatic efficiency in different stages of the photosynthesis reactions.