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.

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.

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.

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.

Iron Oxide Nanoparticles: Biosynthesis, Magnetic Behavior, Cytotoxic Effect.

Iron oxide nanoparticles have attracted much attention because of their superparamagnetic properties and their potential applications in many fields such as magnetic storage devices, catalysis, sensors, superparamagnetic relaxometry (SPMR), and high-sensitivity biomolecule magnetic resonance imaging (MRI) for medical diagnosis and therapeutics. In this study, iron oxide nanoparticles (Fe2 O3 NPs) have been synthesized using a taranjabin (camelthorn or persian manna) aqueous solution. The synthesized Fe2 O3 NPs were identified through powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), field energy scanning electron microscopy (FESEM), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDX), vibrating-sample magnetometer (VSM) and Raman technics. The results show that the nanoparticles have a hexagonal structure with 20 to 60 nm in size. The cytotoxic effect of the synthesized nanoparticles has been tested upon application against lung cancer cell (A549) lines. It was found that there is no cytotoxic activity at lower concentrations of 200 µg/mL. The ability of the synthesized nanoparticles for lead removal in wastewaters was tested. Results show that highest concentration of adsorbent (50 mg/L) has maximum removal efficiency (96.73 %). So, synthesized Fe2 O3 NPs can be a good candidate to use as heavy metals cleaner from contaminated waters.

Environmentally Relevant Iron Oxide Nanoparticles Produce Limited Acute Pulmonary Effects in Rats at Realistic Exposure Levels.

Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeOxNPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeOxNPs present in the environment. We, therefore, analysed the potential toxicity of FeOxNPs of different forms (Fe3O4, α-Fe2O3 and γ-Fe2O3) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeOx-mix). A preliminary in vitro study indicated Fe3O4 and FeOx-mix were more cytotoxic than either form of Fe2O3 in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague-Dawley rats, nose-only exposure, 50 µg/m3 and 500 µg/m3, 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects.

Synthesis and characterization of modified magnetic nanoparticles as theranostic agents: in vitro safety assessment in healthy cells.

Over the past few decades nanotechnology has paved its way into cancer treatment procedures with the use of nanoparticles (NPs) for contrast media and therapeutic agents. Iron based NPs are the most investigated since they can be used for drug delivery, imaging and when magnetically activate employed as local heat sources in cancer hyperthermia. In this work, was performed synthesis, characterization and biological evaluation of different types of iron oxide nanoparticles (mNPs'), as promising material for tumor hyperthermia. The surface of mNPs' has modified with inorganic stabilizing agents to particularly improve characteristics such as their magnetic properties, colloidal stability and biocompatibility. The successful coating of mNPs' was confirmed by morphological and structural characterization by transmission electron microscopy (TEM) and Fourier-Transform Infra-Red spectroscopy (FT-IR), while their hydrodynamic diameter was studied by using Dynamic light scattering (DLS). X-ray Diffraction (XRD) proved that the crystallite phase of mNPs' is the same with the pattern of magnetite. Superparamagnetic behavior and mNPs' response under the application of alternating magnetic field (AMF) were also thoroughly investigated and showed good heating efficiency in magnetic hyperthermia experiments. The contrast ability in magnetic resonance imaging (MRI) is also discussed indicating that mNPs are negative MRI contrast types. Nonetheless the effects of mNPs on cell viability was performed by MTT on human keratinocytes, human embryonic kidney cells, endothelial cells and by hemolytic assay on erythrocytes. In healthy keratinocytes wound healing assay in different time intervals was performed, assessing both the cell migration and wound closure. Endothelial cells have also been studied in functional activity performing capillary morphogenesis. In vitro studies showed that mNPs are safely taken by the healthy cells and do not interfere with the biological processes such as cell migration and motility.

Accumulation and cytotoxicity assessment of TAT-IONPs on cancerous mammalian cells.

Nanotechnology is a fast-growing research technology. Nanoparticles have intensive scientific applications in many fields. Depending on the physical and chemical characteristics of a nanoparticle, it can be used either as a treatment agent to fight disease or as a delivery vehicle to transport the therapeutic drug to a specified biological organ, tissue, and cell. Cytotoxicity evaluation of nanoparticles is one of the primary concerns in clinical practices to avoid unpredicted or undesirable interactions that could worsen the case. Iron oxide nanoparticle (IONP) is the most utilized nanoparticle in medical fields for treatment, diagnostic, and imaging. This paper is designated to investigate the cytotoxicity of IONPs that decorated with Trans-Activator of Transcription (TAT) protein. WST-1 assay and flow cytometry were used to assess the cytotoxicity of TAT-IONPs, which showed no significant cytotoxic effect on mammalian breast cancer cells (MCF-7). Nanoparticles accumulation in the cell's cytoplasm was evaluated from TEM images by measuring the size of the endosome. The results indicate that TAT-IONPs can be used as a safe and non-toxic nanoplatform for targeted delivery at 50 µg/ml or less. Also, they present an approach by which the area of intracellular endosome can be assessed from the TEM images of fixed cells. In this study, the endosome size increased in a time-dependent manner.

Co-exposure of iron oxide nanoparticles and glyphosate-based herbicide induces DNA damage and mutagenic effects in the guppy (Poecilia reticulata).

Iron oxide nanoparticles (IONPs) have been tested to remediate aquatic environments polluted by chemicals, such as pesticides. However, their interactive effects on aquatic organisms remain unknown. This study aimed to investigate the genotoxicity and mutagenicity of co-exposure of IONPs (γ-Fe2O3 NPs) and glyphosate-based herbicide (GBH) in the fish Poecilia reticulata. Thus, fish were exposed to citrate-functionalized γ-Fe2O3 NPs (0.3 mg L-1; 5.44 nm) alone or co-exposed to γ-Fe2O3 NPs (0.3 mg L-1) and GBH (65 and 130 µg of glyphosate L-1) during 14 and 21 days. The genotoxicity (DNA damage) was analyzed by comet assay, while the mutagenicity evaluated by micronucleus test (MN test) and erythrocyte nuclear abnormalities (ENA) frequency. The co-exposure induced clastogenic (DNA damage) and aneugenic (nuclear alterations) effects on guppies in a time-dependent pattern. Fish co-exposed to NPs and GBH (130 µg glyphosate L-1) showed high DNA damage when compared to NPs alone and control group, indicating synergic effects after 21 days of exposure. However, mutagenic effects (ENA) were observed in the exposure groups after 14 and 21 days. Results showed the potential genotoxic and mutagenic effects of maghemite NPs and GBH co-exposure to freshwater fish. The transformation and interaction of iron oxide nanoparticles with other pollutants, as herbicides, in the aquatic systems are critical factors in the environmental risk assessment of metal-based NPs.

A biocompatible theranostic nanoplatform based on magnetic gadolinium-chelated polycyclodextrin: in vitro and in vivo studies.

A novel theranostic nanoplatform was prepared based on Fe3O4 nanoparticles (NPs) coated with gadolinium ions decorated-polycyclodextrin (PCD) layer (Fe3O4@PCD-Gd) and employed for Curcumin (CUR) loading. The dissolution profile of CUR indicated a pH sensitive release manner. Fe3O4@PCD-Gd NPs exhibited no significant toxicity against both normal and cancerous cell lines (MCF 10A and 4T1, respectively); while the CUR-free NPs showed more toxicity against 4T1 than MCF 10A cells. In vivo anticancer study revealed appropriate capability of the system in tumor shrinking with no tissue toxicity and adverse effect on body weight. In vivo MR imaging of BALB/c mouse showed both T1 and T2 contrast enhancement on the tumor cells. Fe3O4@PCD-Gd/CUR NPs showed significant features as a promising multifunctional system having appropriate T1-T2 dual contrast enhancement and therapeutic efficacy in cancer theranostics.

In vitro cytotoxicity of co-exposure to superparamagnetic iron oxide and solid lipid nanoparticles.

Increased production and use of different types of nanoparticles (NPs) in the last decades has led to increased environmental release of these NPs with potential detrimental effects on both the environment and public health. Information is scarce in the literature on the cytotoxic effect of co-exposure to many NPs as this concern is relatively recent. Thus, in this study, we hypothesized scenarios of cell's co-exposure to two kinds of NPs, solid lipid nanoparticles (SLNs) and superparamagnetic iron oxide nanoparticles (SPIONs), to assess the potential cytotoxicity of exposure to NPs combination. Cytotoxicity of SPIONs, SLNs, and their 1:1 mixture (MIX) in six tumor and six non-tumor cell lines was investigated. The mechanisms underlining the induced cytotoxicity were studied through cell cycle analysis, detection of reactive oxygen species (ROS), and alterations in mitochondrial membrane potential (ΔΨM). Double staining with acridine orange and ethidium bromide was also used to confirm cell morphology alterations. The results showed that SPIONs induced low cytotoxicity compared to SLNs. However, the mixture of SPIONs and SLNs showed synergistic, antagonistic, and additive effects based on distinct tests such as viability assay, ROS generation, ΔΨM, and DNA damage, depending on the cell line. Apoptosis triggered by ROS and disturbances in ΔΨM are the most probable related mechanisms of action. As was postulated, there is possible cytotoxic interaction between the two kinds of NPs.

Disruption of Cell Adhesion and Cytoskeletal Networks by Thiol-Functionalized Silica-Coated Iron Oxide Nanoparticles.

One of the major obstacles that limits the use of magnetic nanoparticles in biomedical applications is their potential toxicity. In the present study, we evaluated the cytotoxic effects of thiol-functionalized silica-coated iron oxide (Fe3O4@SiO2-SH) nanoparticles using human lung epithelial cells A549. We investigated the effect of Fe3O4@SiO2-SH nanoparticles on the cell viability, proliferation, cell cycle distribution, adhesion, apoptosis, and the orientation of the cytoskeletal networks, as well as on expression of proteins involved in cell death, cell survival, and cell adhesion. We demonstrated that exposure of A549 cells to Fe3O4@SiO2-SH nanoparticles resulted in severe disruption of the actin microfilaments and microtubule cytoskeleton and reduced the size of focal adhesions. Furthermore, cell adhesion was significantly affected as well as the phosphorylation of focal adhesion kinase (FAK), extracellular-signal-regulated kinase (ERK), and p38. Our findings highlight the need for in-depth cytotoxic evaluation of nanoparticles supporting their safer use, especially in biomedical applications.