Effects of multi-walled carbon nanotubes and halloysite nanotubes on plasma lipid profiles and autophagic lipolysis pathways in mouse aortas and hearts.

Multi-walled carbon nanotubes (MWCNTs) and halloysite nanotubes (HNTs) are widely used tubular-structured nanomaterials (NMs), but their cardiovascular effects are not clear. This study compared the effects of MWCNTs and HNTs on lipid profiles in mouse plasma and gene expression profiles in aortas and hearts. Mice were intravenously injected with 50 µg NMs, once a day, for 5 days. Then, the plasma was collected for lipidomics analysis, and aortas and hearts were collected for RNA-sequencing analysis. While MWCNTs or HNTs did not induce obvious pathological changes in aortas or hearts, the lipid profiles in mouse plasma were altered. Further analysis revealed that MWCNTs more effectively upregulated sphingolipids and sterol lipids, whereas HNTs more effectively upregulated glycerophospholipids and fatty acyls. Consistently, RNA-sequencing data indicated that MWCNTs and HNTs altered signaling pathways related with lipid synthesis and metabolism, as well as those related with endoplasmic reticulum, lysosomes and autophagy, more significantly in aortas than in hearts. We further verified the changes of proteins involved in autophagic lipolysis, that MWCNTs were more effectively to suppress the autophagic biomarker LC3, whereas HNTs were more effectively to affect lipid metabolism proteins. These results may provide novel understanding about the influences of MWCNTs and HNTs on lipid profiles and lipid signaling pathways in cardiovascular systems. Importantly, previous studies considered HNTs as biocompatible materials, but the results from this study suggested that both MWCNTs and HNTs were capable to affect lipid profiles and autophagic lipolysis pathways in cardiovascular systems, although their exact influences were different.

Influence of Impurities from Manufacturing Process on the Toxicity Profile of Boron Nitride Nanotubes.

The toxicity of boron nitride nanotubes (BNNTs) has been the subject of conflicting reports, likely due to differences in the residuals and impurities that can make up to 30-60% of the material produced based on the manufacturing processes and purification employed. Four BNNTs manufactured by induction thermal plasma process with a gradient of BNNT purity levels achieved through sequential gas purification, water and solvent washing, allowed assessing the influence of these residuals/impurities on the toxicity profile of BNNTs. Extensive characterization including infrared and X-ray spectroscopy, thermogravimetric analysis, size, charge, surface area, and density captured the alteration in physicochemical properties as the material went through sequential purification. The material from each step is screened using acellular and in vitro assays for evaluating general toxicity, mechanisms of toxicity, and macrophage function. As the material increased in purity, there are more high-aspect-ratio particulates and a corresponding distinct increase in cytotoxicity, nuclear factor-κB transcription, and inflammasome activation. There is no alteration in macrophage function after BNNT exposure with all purity grades. The cytotoxicity and mechanism of screening clustered with the purity grade of BNNTs, illustrating that greater purity of BNNT corresponds to greater toxicity.

In vitro and in vivo MRI imaging and photothermal therapeutic properties of Hematite (α-Fe2O3) Nanorods.

Herein we report synthesis of hematite (α-Fe2O3) nanorods by calcinating hydrothermally synthesized goethite nanorods at 5000C. The structural, optical and MRI imaging guided cancer therapeutic properties of fabricated nanorods have been discussed in this manscript. FESEM and TEM imaging techniques were used to confirm the nanorod like morphology of as prepared materials. As we know that Fe2O3 nanorods with size in the range of 25-30 nm exhibit super magnetism. After coating with the PEG, the as prepared nanorods can be used as T2 MR imaging contrast agents. An excellent T2 MRI contrast of 38.763 mM-1s-1 achieved which is highest reported so far for α-Fe2O3. Besides the as prepared nanorods display an excellent photothermal conversion efficiency of 39.5% thus acts as an excellent photothermal therapeutic agent. Thus, we envision the idea of testing our nanorods for photothermal therapy and MR imaging application both in vitro and in vivo, achieving an excellent T2 MRI contrast and photothermal therapy effect with as prepared PEGylated nanorods.

The role of mitochondrial dynamics in the TiO2 nanotube-accelerated osteogenic differentiation of MC3T3-E1 cells.

Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells.

Preparation, toxicity reduction and radiation therapy application of gold nanorods.

Gold nanorods (GNRs) have a broad application prospect in biomedical fields because of their unique properties and controllable surface modification. The element aurum (Au) with high atomic number (high-Z) render GNRs ideal radiosensitive materials for radiation therapy and computed tomography (CT) imaging. Besides, GNRs have the capability of efficiently converting light energy to heat in the near-infrared (NIR) region for photothermal therapy. Although there are more and more researches on GNRs for radiation therapy, how to improve their biocompatibility and how to efficiently utilize them for radiation therapy should be further studied. This review will focuse on the research progress regarding the preparation and toxicity reduction of GNRs, as well as GNRs-mediated radiation therapy.

The Effect of Surface-Modified Gold Nanorods on the Early Stage of Embryonic Development and Angiogenesis: Insight into the Molecular Pathways.

Gold nanorods have been implicated in several biomedical applications. Herein, the effect of two surface-modified gold nanorods on the early stages of embryogenesis and angiogenesis was investigated using avian embryos at three days and their chorioallantoic membrane (CAM) at five days of incubation. We found that gold nanorods (GNR) modified with PEGylated phospholipid moiety show a high mortality rate in embryos after four days of exposure compared to GNR modified with PEGylated cholesterol moiety. Meanwhile, our data revealed that surface modified-GNR significantly inhibit the formation of new blood vessels in the treated CAM model after 48 h of exposure. Moreover, we report that surface-modified GNR significantly deregulate the expression of several genes implicated in cell proliferation, invasion, apoptosis, cellular energy metabolism, and angiogenesis. On the other hand, our data point out that GNR treatments can modulate the expression patterns of JNK1/2/3, NF-KB/p38, and MAPK, which could be the main molecular pathways of the nanorods in our experimental models.

Single-Cell Adenosine Triphosphate Content Monitoring during Hyperthermia Cell Death by Using Plasmonic Fluorescent Nanoflare.

Gold nanorods-based plasmonic photothermal therapy (AuNRs-PPTT) is a prospective anticancer approach in which AuNRs absorb near-infrared (NIR) light and convert it into heat, leading to cell death. Investigating the molecular energy metabolism of single cells, especially cancer cells, during the hyperthermia cell death process is therefore of great significance, as it can help us to better understand the photothermal lethal mechanism of cancer cells and design new photothermal probes more rationally. However, during the AuNRs-PPTT process, how the cells respond to heat stimulation and how their energy metabolism changes have rarely been studied. Herein, we selected adenosine triphosphate (ATP) as a target molecule, and by preparing a plasmonic and turn-on type fluorescent nanoprobe, we examined the ATP metabolism difference between cancerous cells and normal cells during the AuNRs-PPTT process. We found that the fluorescence intensity increased ∼60% after 5 min laser irradiation as compared to the initial intensity in single HeLa cells, but only ∼20% increase was observed for single H8 cells; obviously, the increase of ATP content in cancerous cells was notably higher than that in normal cells during the hyperthermia cell death.

The aspect ratio of gold nanorods as a cytotoxicity factor on Raphidocelis subcaptata.

Gold nanorods (AuNRs) are promising nanoscale materials for several technological and biomedical applications. The physicochemical properties of AuNRs, including size, shape and surface features, are crucial factors affecting their cytotoxicity. In this study, we investigated the effects of different aspect ratios of AuNRs (1.90, 2.35, 3.25 and 3.50) at concentrations of 2 and 10 µg mL-1 on their cytotoxicity and cellular uptake in green algae Raphidocelis subcaptata. The experiment was performed in oligotrophic freshwater medium in a growth chamber with constant agitation of 80 rpm under controlled conditions (120 µEm-2s-1 illumination; 12:12h light dark cycle and constant temperature of 22 ± 2 °C). The algal growth was monitored daily for 96 h via electronic absorbance scanning at 600-750 nm. Oxidative stress, cell viability and autofluorescence were evaluated using a flow cytometer. Oxidative stress quantified by loading cultures with the fluorescent dye 2', 7'-dichlorofluorescein diacetate. To assess algal cell viability, propidium iodide was selected as the fluorescent probe. Our results indicated that the aspect ratio of AuNRs mediates their biological effects in green algae R. subcaptata. A positive correlation between oxidative stress and increase of aspect ratio was found at concentration of 10 µg mL-1. Higher cytotoxicity and mortality were observed for algae incubated with higher aspect ratios AuNRs (3.50). These findings may be useful to understand the impact of the AuNRs in aquatic environments, contributing to ecosystem management and nanomaterials regulation.

An in vivo study of nanorod, nanosphere, and nanowire forms of titanium dioxide using Drosophila melanogaster: toxicity, cellular uptake, oxidative stress, and DNA damage.

The biological impact of nanomaterials (NMs) is determined by several factors such as size and shape, which need to be taken into consideration in any type of analysis. While investigators often prefer to conduct in vitro studies for detection of any possible adverse effects of NMs, in vivo approaches yield more relevant data for risk assessment. For this reason, Drosophila melanogaster was selected as a suitable in vivo model to characterize the potential risks associated with exposure nanorods (NRs), nanospheres (NSs), nanowires (NWs) forms of titanium dioxide (TiO2), and their microparticulated (or bulk) form, as TiO2. Third instar larvae (72 hr old larvae) were fed with TiO2 (NRs, NSs, or NWs) and TiO2 at concentrations ranging from 0.01 to 10 mM. Viability (toxicity), internalization (cellular uptake), intracellular reactive oxygen species (ROS) production, and genotoxicity (Comet assay) were the end-points evaluated in hemocyte D. melanogaster larvae. Significant intracellular oxidative stress and genotoxicity were noted at the highest exposure concentration (10 mM) of TiO2 (NRs, NSs, or NWs), as determined by the Comet assay and ROS analysis, respectively. A concentration-effect relationship was observed in hemocytes exposed to the NMs. Data demonstrated that selected forms of TiO2.-induced genotoxicity in D. melanogaster larvae hemocytes indicating this organism is susceptible for use as a model to examine in vivo NMs-mediated effects.

Changing the morphology of one-dimensional titanate nanostructures affects its tissue distribution and toxicity.

The present research investigated the impact of the morphology change of titanate (TiO2) nanostructures on its tissue distribution and toxicity. The TiO2 nanotubes, rods, and ribbons were synthesized by the hydrothermal technique, and the morphology was adjusted by alteration of the hydrothermal duration time. The characterization techniques were X-ray diffraction, high-resolution transmission electron microscopy, dynamic light scattering, and the Brunauer-Emmett-Teller method for measuring the surface area. The intravenously administrated dose (5 mg/kg) was injected as a single dose for 1 day and consecutively for 42 days. The quantitative analysis of accumulated TiO2 nanostructures in the liver, spleen, and the heart was performed using an inductively coupled plasma emission spectrometer, and the organs' toxicity was estimated by histopathological analysis. The prepared nanostructures exhibited differences in morphology, crystallinity, size distribution, surface area, zeta potential, and aspect ratio. The results revealed a tissue distribution difference between the liver, spleen, and heart of these nanostructures, the distribution order was the liver, spleen, and the heart for all TiO2 nanostructures. The toxicity was induced with different degrees. The nanotubes were the most harmful among the three formats. In summary, changes in the morphology of the TiO2 nanostructures change its distribution and toxicity.

PEGylated gold nanorods are not cytotoxic to human endothelial cells but affect kruppel-like factor signaling pathway.

Gold (Au) nanomaterials (NMs), particularly those with PEG surface functionalization, are generally considered to be biocompatible for biomedical applications due to relatively low cytotoxicity. Herein, we investigated the toxicity of PEGylated Au nanorods (NRs) to human umbilical vein endothelial cells (HUVECs), a commonly used in vitro model for human endothelium. We found a previously unknown effect that up to 10 µg/mL Au NRs, albeit not cytotoxic, decreased the mRNA and protein levels of kruppel-like factor 2 (KLF2), a transcription factor with well-documented vasoprotective effects. The results from PCR array showed that a number of genes associated with risk of cardiovascular diseases were altered by Au NRs, and several genes are downstream genes of KLF2 according to ingenuity pathway analysis (IPA). These effects could be observed with or without the presence of inflammatory stimuli lipopolysaccharide (LPS), which suggests a pre-existing inflammatory state is not required for Au NRs to alter KLF2 signaling pathway. We further identified that Au NRs significantly decreased eNOS mRNA/p-eNOS proteins as well as increased MCP-1 mRNA/sMCP-1 release, which are targets of KLF2. Combined, our data revealed a novel pathway that PEGylated Au NPs at non-cytotoxic concentrations might alter KLF leading to the increase of risk of cardiovascular diseases in human endothelial cells. Given the importance of KLF in vascular homeostasis, our data indicate that it is necessary to evaluate the influence of engineered NPs to KLF signaling pathways, especially for NPs with biomedical uses.

Insights into the Cellular Uptake, Cytotoxicity, and Cellular Death Modality of Phospholipid-Coated Gold Nanorods toward Breast Cancer Cell Lines.

Gold nanorods (GNRs) have gained pronounced recognition in the diagnosis and treatment of cancers driven by their distinctive properties. Herein, a gold-based nanosystem was prepared by utilizing a phospholipid moiety linked to thiolated polyethylene glycol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-PEG-SH, as a surface decorating agent. The synthesized phospholipid-PEG-GNRs displayed good colloidal stability upon exposure to the tissue culture medium. Cytotoxicity of phospholipid-PEG-GNRs was investigated toward MCF-7 and T47D breast cancer cells using sulforhodamine B test. The results revealed that phospholipid-PEG-GNRs demonstrated  high cytotoxicity to MCF-7 cells compared to T47D cells, and minimal cytotoxicity to human dermal fibroblasts. The cellular uptake studies performed by imaging and quantitative analysis demonstrated  massive internalization of phospholipid-coated GNRs into  MCF-7 cells in comparison to T47D cells. The cellular death modality of cancer cells after treatment with phospholipid-PEG-GNRs was evaluated using mitochondrial membrane potential assay (JC-1 dye), gene expression analysis, and flow cytometry study. The overall results suggest that phospholipid-modified GNRs enhanced mainly the cellular apoptotic events in MCF-7 cells in addition to necrosis, whereas cellular necrosis and suppression of cellular invasion contributed to the cellular death modality in the T47D cell line upon treatment with phospholipid-PEG-GNRs. The phospholipid-coated GNRs interact in a different manner with breast cancer cell lines and could be considered for breast cancer treatment.

BMP-2-Loaded HAp:Ln3+ (Ln = Yb, Er, Gd) Nanorods with Dual-Mode Imaging for Efficient MC3t3-E1 Cell Differentiation Regulation.

Effective bone tissue reconstitution improves the treatment success rate of dental implantation and preserves natural teeth during periodontal tissue repair. Hydroxyapatite (HAp) has received much attention in bone remodeling field because its mineralized structure is similar to that of the natural bone tissue. For this reason, it has been used as a carrier for growth factors. Although HAp possesses outstanding biomedical properties, its capacity of loading and releasing bone growth factors and promoting osteogenesis is not well understood. In this study, Ln3+ (Ln = Yb3+, Er3+, Gd3+)-doped HAp (HAp:Ln3+) nanorods were synthesized by one-step hydrothermal method. To improve its biocompatibility and surface properties, bone morphogenetic protein-2 (BMP-2) was loaded onto the surface of HAp:Ln3+ nanorods. The results showed that BMP-2 incorporation promoted bone formation and enhanced the expression of early bone-related gene and protein (RunX2, SP7, OPN). In addition, Yb3+- and Er3+-doped HAp nanorods were examined by upconversion luminescence with 980 nm near-infrared laser irradiation to monitor the delivery position of BMP-2 protein. Furthermore, due to the positive magnetism correlated with the concentration of Gd3+, HAp:Ln3+ with enhanced contrast brightening can be deemed as T1 MIR contrast agents. These findings indicate that HAp doped with rare-earth ions and loaded with BMP-2 has the potential to promote bone tissue repair and execute dual-mode imaging.

The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles.

Understanding the possible role of physicochemical properties in determining the toxicity of ZnO nanomaterials (NMs) is crucial for the safe use of ZnO-based materials. In this study, we synthesized four types of ZnO NMs, and characterized them as ZnO nanorods (NRs; length 400-500 nm, diameter 150-200 nm), ZnO Mini-NRs (length 50-100 nm, diameter 15-20 nm), amorphous ZnO microspheres (a-ZnO MS) and crystalline ZnO MS (c-ZnO MS; the a/c-ZnO MS are nanoflowers with an extensive growth of sheet-like structures). ZnO NMs and ZnO Mini-NRs were significantly more cytotoxic than a/c-ZnO MS, and this trend was similar in both HepG2 cells and human umbilical vein endothelial cells. Intracellular reactive oxygen species was only modestly induced by c-ZnO MS, whereas intracellular Zn ions were dose-dependently increased in HepG2 cells by the exposure of all types of ZnO NMs. The expression of endoplasmic reticulum stress marker DDIT3 was induced following an order of ZnO NRs > a-ZnO MS > c-ZnO MS > ZnO Mini-NRs, and the apoptosis gene CASP12 was induced following an order of a-ZnO MS > ZnO NRs > c-ZnO MS > ZnO Mini-NRs. Combined, these results suggested that ZnO NM-induced cytotoxicity and expression of endoplasmic reticulum stress-apoptosis genes could be influenced by the size and shape of ZnO NMs.

Ultrasensitive "FRET-SEF" Probe for Sensing and Imaging MicroRNAs in Living Cells Based on Gold Nanoconjugates.

MicroRNAs (miRNAs), a kind of single-stranded small RNA molecule, play significant roles in the physiological and pathological processes of human beings. Currently, miRNAs have been demonstrated as important biomarkers critically related to many diseases and life nature, including several cancers and cell senescence. It is valuable to establish sensitive assays for monitoring the levels of intracellular up-regulated/down-regulated miRNA expression, which would contribute to the early prediction of the tumor risk and cardiovascular disease. Here, an oriented gold nanocross (AuNC)-decorated gold nanorod (AuNR) probe with "OFF-enhanced ON" fluorescence switching was developed based on fluorescence resonance energy transfer and surface enhanced fluorescence (FRET-SEF) principle. The nanoprobe was used to specifically detect miRNA in vitro, which gave two linear responses represented by the equation F = 1830.32 log C + 6349.27, R2 = 0.9901, and F = 244.41 log C + 1916.10, R2 = 0.9984, respectively, along with a detection limit of 0.5 aM and 0.03 fM, respectively. Furthermore, our nanoprobe was used to dynamically monitor the expression of intracellular up-regulated miRNA-34a from the HepG2 and H9C2 cells stimulated by AFB1 and TGF-ß1, and the experimental results showed that the new probe not only could be used to quantitively evaluate miRNA oncogene in vitro, but also enabled tracking and imaging of miRNAs in living cells.

In vitro interaction and biocompatibility of titanate nanotubes with microglial cells.

Titanate nanotubes (TiONts) are promising agents for biomedical applications. Microglial activation and associated oxidative burst are major challenges in drug delivery applications across the brain. Here, TiONts were designed for drug delivery systems by functionalizing them with (3-aminopropyl) triethoxysilane (APTES), their interactions and biocompatibility were studied in vitro using murine microglial BV-2 cells. TiONts-APTES exposure resulted in increased ROS production and transient mitochondrial hyperpolarization. However, there was no indication of microglial proliferation in BV-2 cells as suggested by cell cycle analysis and morphology evaluation. The endocytosis as well as passive diffusion mediated TiONts-APTES internalization were proved by transmission electron microscopy (TEM) with and without amiloride, an endocytosis inhibiting agent. In addition, the TiONts-APTES exhibited good biocompatibility on microglial BV-2 cells as revealed by the plasma membrane integrity, lysosmal membrane integrity, morphology and viability analysis.

Effects of differently shaped TiO2NPs (nanospheres, nanorods and nanowires) on the in vitro model (Caco-2/HT29) of the intestinal barrier.

BACKGROUND: The biological effects of nanoparticles depend on several characteristics such as size and shape that must be taken into account in any type of assessment. The increased use of titanium dioxide nanoparticles (TiO2NPs) for industrial applications, and specifically as a food additive, demands a deep assessment of their potential risk for humans, including their abilities to cross biological barriers. METHODS: We have investigated the interaction of three differently shaped TiO2NPs (nanospheres, nanorods and nanowires) in an in vitro model of the intestinal barrier, where the coculture of Caco-2/HT29 cells confers inherent intestinal epithelium characteristics to the model (i.e. mucus secretion, brush border, tight junctions, etc.). RESULTS: Adverse effects in the intestinal epithelium were detected by studying the barrier's integrity (TEER), permeability (LY) and changes in the gene expression of selected specific markers. Using Laser Scanning Confocal Microscopy, we detected a different behaviour in the bio-adhesion and biodistribution of each of the TiO2NPs. Moreover, we were able to specifically localize each type of TiO2NPs inside the cells. Interestingly, general DNA damage, but not oxidative DNA damage effects, were detected by using the FPG version of the comet assay. CONCLUSIONS: Results indicate different interactions and cellular responses related to differently shaped TiO2NPs, nanowires showing the most harmful effects.

Polylysine as a functional biopolymer to couple gold nanorods to tumor-tropic cells.

BACKGROUND: The delivery of plasmonic particles, such as gold nanorods, to the tumor microenvironment has attracted much interest in biomedical optics for topical applications as the photoacoustic imaging and photothermal ablation of cancer. However, the systemic injection of free particles still crashes into a complexity of biological barriers, such as the reticuloendothelial system, that prevent their efficient biodistribution. In this context, the notion to exploit the inherent features of tumor-tropic cells for the creation of a Trojan horse is emerging as a plausible alternative. RESULTS: We report on a convenient approach to load cationic gold nanorods into murine macrophages that exhibit chemotactic sensitivity to track gradients of inflammatory stimuli. In particular, we compare a new model of poly-L-lysine-coated particles against two alternatives of cationic moieties that we have presented elsewhere, i.e. a small quaternary ammonium compound and an arginine-rich cell-penetrating peptide. Murine macrophages that are exposed to poly-L-lysine-coated gold nanorods at a dosage of 400 µM Au for 24 h undertake efficient uptake, i.e. around 3 pg Au per cell, retain the majority of their cargo until 24 h post-treatment and maintain around 90% of their pristine viability, chemotactic and pro-inflammatory functions. CONCLUSIONS: With respect to previous models of cationic coatings, poly-L-lysine is a competitive solution for the preparation of biological vehicles of gold nanorods, especially for applications that may require longer life span of the Trojan horse, say in the order of 24 h. This biopolymer combines the cost-effectiveness of small molecules and biocompatibility and efficiency of natural peptides and thus holds potential for translational developments.

Assessment of oxidative stress induced by gold nanorods following intra-tracheal instillation in rats.

Gold nanorods (GNRs) are used for their wide variety of applications in various industries. There is a little availability of data related to toxicity and ecological implications of these GNRs. The study evaluated the oxidative stress induction following intra-tracheal instillation of 1 and 5 mg/kg b.w. doses of 10 and 25 nm GNRs by estimating various oxidative stress markers including lipid peroxidation (malondialdehyde; MDA), glutathione (GSH), superoxide dismutase (SOD), catalase and total antioxidant capacity (TAC) after 1 day, 1 week, 1 month, and 3 months post exposure periods. The results have shown increased MDA levels and decreased GSH levels following 1 day and 1 week post exposure periods, indicating induction of oxidative stress. Also, the SOD, catalase and TAC levels were significantly decreased following exposure of both 10 and 25 nm GNRs after 1 day and 1 week after exposures, indicating the inhibition of antioxidant defense mechanisms. Moreover, the 10 nm GNRs at 5 mg/kg dose displayed greater changes in all the estimated parameters, representing dose and size based induction of oxidative stress by GNRs. In contrast, a little change was observed during 1 month and 3 months post exposure periods, may be due to recovery. Finally, the GNRs induced dose-size-dependent oxidative stress induction by various oxidative stress markers following intra-tracheal instillation in rats.

Halloysite nanotubes-induced Al accumulation and oxidative damage in liver of mice after 30-day repeated oral administration.

Halloysite (Al2 Si2 O5 (OH)4 ·nH2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury.