Bioaccessibility as a determining factor in the bioavailability and toxicokinetics of cadmium compounds.

Cadmium toxicity occurs where there is absorption and accumulation of cadmium ions (Cd2+) in tissues beyond tolerable levels. Significant differences in the release of Cd2+ from cadmium compounds in biological fluids, like gastric fluid, may indicate differences in bioavailability and absorption. This means that direct read-across from high solubility cadmium compounds to lower solubility compounds may not accurately reflect potential hazards. Here, the relative bioaccessibility in gastric fluid of cadmium telluride and cadmium chloride was evaluated using in vitro bioelution tests whilst the toxicokinetic behavior of these two compounds were compared after dietary administration for 90 days in male and female Wistar Han rats following OECD TG 408. Cadmium chloride was highly bioaccessible, whilst cadmium telluride showed low solubility in simulated gastric fluid (90 % and 1.5 % bioaccessibility, respectively). This difference in bioaccessibility was also reflected by a difference in bioavailability as shown by the difference in the liver and kidney concentrations of cadmium after repeat oral exposure. Feeding at doses of 750 and 1500 ppm of cadmium telluride did not result in tissue cadmium levels above the lower limit of quantification (LLOQ). In contrast, feeding with a lower test substance concentration yet higher concentration of bioaccessible cadmium (30 ppm cadmium chloride) resulted in tissue accumulation of cadmium. Only slight, non-adverse changes in hematology and clinical chemistry parameters were seen at these doses, indicating an absence of significant cadmium mediated toxicity towards target organs (kidney and liver), reflected in minimal cadmium accumulation in these organs. This study demonstrates that bioelution tests can help determine the bioaccessibility of cadmium, which can be used to estimate the potential for target tissue toxicity based on known toxicokinetic profiles and threshold levels for cadmium toxicity, while reducing and refining animal testing.

Strong accumulation capacity of hyperaccumulator Solanum nigrum L. for low or insoluble Cd compounds in soil and its implication for phytoremediation.

This experiment is to explore whether one hyperaccumulator shows the strongly accumulative capacities for low or insoluble Cd compounds in soil. Soil potting experiment was conducted to analyze the accumulation capacity of Solanum nigrum L. for 10 different Cd compounds under two levels. The results clearly indicated: The Cd concentrations of shoots and roots were very high for different Cd compounds in soils even with low or insoluble Cd compounds compared with easily soluble Cd in the treatments of soil contaminated with Cd at different concentrations. Furthermore, the EFs and TFs were all larger than 1 either. Based on the results, although the bioavailabilities of some Cd compounds in soil were lower, S. nigrum's ability to accumulate them was still very strong. Phytoremediation may be widely used to treat with soil contaminated by different cadmium compounds. In addition, the total Cd content is also very important in evaluating the risk of Cd contamination in soil. Thus, phytoextraction is promising.

A new method for evaluating the bioaccessibility of different foodborne forms of cadmium.

The bioabsorption and biotoxicity of cadmium are closely related to its binding form. Currently, total concentration is used as the indicator for evaluating cadmium toxicity in food, but it might not accurately reflect cadmium's toxic effects. This study attempted to evaluate the toxicity of the different forms of cadmium including cadmium-malate, cadmium-glutathione, and cadmium-metallothionein that are commonly found in food. The in vitro physiologically based extraction test (PBET) combined with Visual MINTEQ modeling was used to predict the toxicity of different forms of cadmium, and acute toxicity testing was performed in mice for validating their results. The in vivo experimental results showed that different forms of cadmium had diverse biotoxicities of which PBET was a good predictor. In particular, the simulation of cadmium ions in PBET using the MINTEQ software revealed that the free cadmium ion content in the simulated intestinal fluid had a superior linear relationship than the total cadmium concentration with the toxicology indexes. Verification using the other two forms of cadmium confirmed the accuracy of the prediction of their biotoxicity. These findings hopefully provide an important reference for a more accurate and rapid safety assessment of cadmium in food.

Biodistribution and Systemic Effects in Mice Following Intravenous Administration of Cadmium Telluride Quantum Dot Nanoparticles.

Quantum dots (QDs) are engineered nanoparticles (NPs) of semiconductor structure that possess unique optical and electronic properties and are widely used in biomedical applications; however, their risks are not entirely understood. This study investigated the tissue distribution and toxic effects of cadmium telluride quantum dots (CdTe-QDs) in male BALB/c mice for up to 1 week after single-dose intravenous injections. CdTe-QDs were detected in the blood, lung, heart, liver, spleen, kidney, testis and brain. Most CdTe-QDs accumulated in the liver, followed by the spleen and kidney. At high doses, exposure to CdTe-QDs resulted in mild dehydration, lethargy, ruffled fur, hunched posture, and body weight loss. Histological analysis of the tissues, upon highest dose exposures, revealed hepatic hemorrhage and necrotic areas in the spleen. The sera of mice treated with high doses of CdTe-QDs showed significant increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels, as well as a reduction in albumin. CdTe-QD exposure also led to a reduced number of platelets and elevated total white blood cell counts, including monocytes and neutrophils, serum amyloid A, and several pro-inflammatory cytokines. These results demonstrated that the liver is the main target of CdTe-QDs and that exposure to CdTe-QDs leads to hepatic and splenic injury, as well as systemic effects, in mice. By contrast, cadmium chloride (CdCl2), at an equivalent concentration of cadmium, appeared to have a different pharmacokinetic pattern from that of CdTe-QDs, having minimal effects on the aforementioned parameters, suggesting that cadmium alone cannot fully explain the toxicity of CdTe-QDs.

Evaluation of Quantum Dot Skin Penetration in Porcine Skin: Effect of Age and Anatomical Site of Topical Application.

BACKGROUND: Pig skin is a widely acknowledged surrogate for human skin for in vitro/ex vivo skin penetration studies with application for small molecules and nanosystems. We have investigated the influence of biological factors such as age and anatomical site on the penetration and distribution of nanoparticles (2.1 nm hydrophilic CdTe/CdS quantum dots: QDs) in adult pig skin (APS), weanling pig skin (WPS) and newborn pig skin (NBPS) at two different anatomical sites (ear and abdomen). METHODS: QDs in saline were applied to 1 × 1 cm2 skin (62.5 pmol/cm2) with 2-min finger rubbing using a standardized protocol. After 6- or 24-h incubation on Franz diffusion cells, tape stripping (×10) followed by manual follicular casting was conducted. Cadmium in QDs was quantified using inductively coupled plasma mass spectrometry for all samples. The presence of QDs in similarly treated skin samples was also captured using multiphoton tomography. RESULTS: QDs were mainly localized in hair follicles after 6 and 24 h of exposure with no cadmium detected in the Franz cell receptor compartment regardless of pig age or anatomical site. The amount of QDs deposited in the follicles was similar at 6 h but higher on APS and WPS ears compared to NBPS ears at 24 h. This is associated with the high follicle density and small follicle diameter of the NBPS compared to the smaller density of much larger follicles on the APS. NBPS showed consistent QD distribution for ear and abdomen up to 24 h. CONCLUSIONS: There is minimal penetration of QDs through pig skin. Density and diameter of follicles in association with age of pigs and application site influenced the amount of QDs deposited in follicles. The structure of the stratum corneum, follicle density and diameter of NBPS are similar to human skin suggesting that NBPS is an appropriate model for human skin in the evaluation of topical applications of a range of chemicals including nanosystems.

The role of epicuticular waxes on foliar metal transfer and phytotoxicity in edible vegetables: case of Brassica oleracea species exposed to manufactured particles.

The rapid industrialization and urbanization of intra- and peri-urban areas at the world scale are responsible for the degradation of the quality of edible crops, because of their contamination with airborne pollutants. Their consumption could lead to serious health risks. In this work, we aim to investigate the phytotoxicity induced by foliar transfer of atmospheric particles of industrial/urban origin. Leaves of cabbage plants (Brassica oleracea var. Prover) were contaminated with metal-rich particles (PbSO4 CuO and CdO) of micrometer size. A trichloroacetic acid (TCA) treatment was used to inhibit the synthesis of the epicuticular waxes in order to investigate their protective role against metallic particles toxicity. Besides the location of the particles on/in the leaves by microscopic techniques, photosynthetic activity measurements, genotoxicity assessment, and quantification of the gene expression have been studied for several durations of exposure (5, 10, and 15 days). The results show that the depletion of epicuticular waxes has a limited effect on the particle penetration in the leaf tissues. The stomatal openings appear to be the main pathway of particles entry inside the leaf tissues, as demonstrated by the overexpression of the BolC.CHLI1 gene. The effects of particles on the photosynthetic activity are limited, considering only the photosynthetic Fv/Fm parameter. The genotoxic effects were significant for the contaminated TCA-treated plants, especially after 10 days of exposure. Still, the cabbage plants are able to implement repair mechanisms quickly, and to thwart the physiological effects induced by the particles. Finally, the foliar contamination by metallic particles induces no serious damage to DNA, as observed by monitoring the BolC.OGG1 gene.

Matricidal hatching can induce multi-generational effects in nematode Caenorhabditis elegans after dietary exposure to nanoparticles.

In this study, we investigated multi-generational effects and generation particle transfer in Caenorhabditis elegans following maternal food exposure to core-shell quantum dots. We found that that the Bag of Worms (BOW) phenotype in aged worms induces changes in quantum dot distribution in the parental body, which is related to the inter-generation transfer of these nanoparticles and to their effects in the offspring. To confirm these results we examined a variety of endpoints, namely, survival, reproduction, aging phenotype, oxidative stress, and intestinal fat metabolism. We show that worms born to parents at different times after exposure show different phenotypic effects as a consequence of quantum dot transfer. This evidence of trans-generational transfer and the effects of nanoparticles highlights the complex multi-generational effects and potential safety hazards that can occur under real environmental conditions.

Cadmium Telluride Quantum Dots as a Fluorescence Marker for Adipose Tissue Grafts.

Plastic and reconstructive surgeons increasingly apply adipose tissue grafting in a clinical setting, although the anticipation of graft survival is insecure. There are only few tools for tracking transplanted fat grafts in vivo.Murine adipose tissue clusters were incubated with negatively charged, mercaptoproprionic acid-coated cadmium telluride quantum dots (QDs) emitting in the dark red or near infrared. The intracellular localization of QDs was studied by confocal laser scanning microscopy.As a result, the adipose tissue clusters showed a proportional increase in fluorescence with increasing concentrations (1, 10, 16, 30, 50 nM) of cadmium telluride QDs. Laser scanning microscopy demonstrated a membrane bound localization of QDs. Vacuoles and cell nuclei of adipocytes were spared by QDs. We conclude that QDs were for the first time proven intracellular in adult adipocytes and demonstrate a strong fluorescence signal. Therefore, they may play an essential role for in vivo tracking of fat grafts.

Effect of Nanoparticle Surface Coating on Cell Toxicity and Mitochondria Uptake.

We report on the effect of surface charge and the ligand coating composition of CdSe/ZnS core/shell quantum dot (QD) nanoparticles on human keratinocyte toxicity using fluorescent microscopy, flow cytometry, transmission electron microscopy. Two commonly reported positive charged (cysteamine, polyethylenimine) and two negative charged (glutathione, dihydrolipoic acid) ligands were studied. The QDs were fully characterized by UV-vis absorption spectroscopy, fluorescence emission spectroscopy, dynamic light scattering and zeta potential. Differences in surface coatings and charges were evaluated against cellular uptake, ROS generation, cytotoxicity, and mitochondrial targeting. Results show that the negative charged QDs coated with GSH exhibit excellent water solubility, high quantum yield and low cytotoxicity. Ligand composition is more important in ROS generation than surface charge whereas surface charge is an important driver of cytotoxicity. Most importantly we observe the selective accumulation of glutathione coated QDs in vesicles in the mitochondria matrix. This observation suggests a new strategy for developing mitochondria-targeted nanomaterials for drug/gene delivery.

Ability of the marine bacterium Pseudomonas fluorescens BA3SM1 to counteract the toxicity of CdSe nanoparticles.

UNLABELLED: In the marine environment, bacteria from estuarine and coastal sediments are among the first targets of nanoparticle pollution; it is therefore relevant to improve the knowledge of interactions between bacteria and nanoparticles. In this work, the response of the marine bacterium Pseudomonas fluorescens BA3SM1 to CdSe nanocrystals (CdSe NPs) of 3nm (NP3) and 8nm (NP8) in diameter was evaluated through microscopic, physiological, biochemical and proteomic approaches. Transmission electron microscopy images showed that NP3 were able to penetrate the bacteria, while NP8 were highly concentrated around the cells, embedded in large exopolysaccharides. In our experimental conditions, both CdSe NP sizes induced a decrease in respiration during the stationary growth phase, while only NP8 caused growth retardation and a decrease in pyoverdine production. Proteomic analyses highlighted that the strain responded to CdSe NP toxicity by inducing various defence mechanisms such as cell aggregation, extracellular CdSe NP sequestration, effective protection against oxidative stress, modifications of envelope organization and properties, and cadmium export. In addition, BA3SM1 presented a biosorption capacity of 1.6×10(16)NP3/g dry weight and 1.7×10(15)NP8/g dry weight. This strain therefore appears as a promising agent for NP bioremediation processes. Proteomic data are available via ProteomeXchange with identifier PXD004012. BIOLOGICAL SIGNIFICANCE: To the best of our knowledge, this is the first report focussing on the effects of CdSe colloidal nanocrystals (CdSe NPs) on a marine strain of Pseudomonas fluorescens. CdSe NPs are extensively used in the industry of renewable energies and it is regrettably expected that these pollutants will sometime soon appear in the marine environment through surface runoff, urban effluents and rivers. Bacteria living in estuarine and coastal sediments will be among the first targets of these new pollutants. The pseudomonads are frequently found in these ecosystems. They are involved in several biogeochemical cycles and are known for their high resistance to pollutants. Consequently, this study focussing on the effects of CdSe NPs on the marine strain P. fluorescens BA3SM1 is highly relevant for several reasons. First, it aims at improving knowledge about the interactions between bacteria and NPs. This is fundamental to effectively use NPs against pathogenic bacteria. Secondly, in spite of CdSe NP interactions with the bacterial cells, the strain BA3SM1 can develop various strategies to counteract CdSe NP toxicity and ensure its growth. It exhibits interesting properties to sequester CdSe NPs and it retains its ability to form biofilm. The strain therefore appears as a promising agent for NP bioremediation thanks to biofiltration processes. Finally, this study shows that CdSe NPs of 8nm in diameter cause a decrease in the secretion of siderophore pyoverdine, a secondary metabolite playing a key role in microbial ecology since it drives bacterial survival and competitiveness in ecosystems. Bacteria producing effective siderophores survive better in a Fe-deficient environment where they antagonize the growth of other microbes thought iron deprivation. Furthermore, siderophores are also employed as virulence factors in human pathogenic strains such as P. aeruginosa. Consequently, this study highlights that NPs can impact the secondary metabolism of bacteria with environmental and medical implications. In addition, in this work, Data-Dependant Acquisition (DDA) provided state of the art Mass Spectrometry data by Spectral Counting and MS1 Label-Free. The combination of these two well-known proteomic techniques including manual validations strengthened the identification and quantification of regulated proteins. Moreover, numerous correlations between proteomic analyses and other observations (physiological, biochemical, microscopic) consolidated our interpretations.

Acute toxicity of quantum dots on late pregnancy mice: Effects of nanoscale size and surface coating.

In this study, the effects of cadmium containing QDs (such as CdSe/ZnS and CdSe QDs) and bulk CdCl2 in pregnant mice, their fetuses, and the pregnancy outcomes were investigated. It was shown that although the QDs and bulk CdCl2 were effectively blocked by the placental barrier, the damage on the placenta caused by CdSe QDs still led to fetus malformation, while the mice in CdSe/ZnS QDs treatment group exhibited slightly hampered growth but showed no significant abnormalities. Moreover, the Cd contents in the placenta and the uterus of CdSe QDs and CdSe/ZnS QDs treatment groups showed significantly higher than the CdCl2 treated group which indicated that the nanoscale size of the QDs allowed relative ease of entry into the gestation tissues. In addition, the CdSe QDs more effectively altered the expression levels of susceptive genes related to cell apoptosis, dysplasia, metal transport, cryptorrhea, and oxidative stress, etc. These findings suggested that the nanoscale size of the QDs were probably more important than the free Cd in inducing toxicity. Furthermore, the results indicated that the outer surface shell coating played a protective role in the adverse effects of QDs on late pregnancy mice.

Cadmium sulfide nanoparticles trigger DNA alterations and modify the bioturbation activity of tubificidae worms exposed through the sediment.

To address the impact of cadmium sulfide nanoparticles (CdS NPs) in freshwater ecosystems, aquatic oligochaete Tubifex tubifex were exposed through the sediment to a low dose (0.52 mg of 8 nm in size of CdS NPs/kg) for 20 days using microcosms. Cadmium (Cd) was released from the CdS NPs-contaminated sediment to the water column, and during this period the average concentrations of Cd in the filtered water fraction were 0.026 ± 0.006 µg/L in presence of oligochaetes. Similar experiments with microparticular CdS and cadmium chloride (CdCl2) were simultaneously performed for comparative purposes. CdS NPs exposure triggered various effects on Tubifex worms compared to control, microsized and ionic reference, including modification of genome composition as assessed using RAPD-PCR genotoxicity tests. Bioaccumulation levels showed that CdS NPs were less bioavailable than CdCl2 to oligochaetes and reached 0.08 ± 0.01 µg Cd/g for CdS NPs exposure versus 0.76 ± 0.3 µg Cd/g for CdCl2 exposure (fresh weight). CdS NPs altered worm's behavior by decreasing significantly the bioturbation activity as assessed after the exposure period using conservative fluorescent particulate tracers. This study demonstrated the high potential harm of the CdS nanoparticular form despite its lower bioavailability for Tubifex worms.

In vivo study of immunogenicity and kinetic characteristics of a quantum dot-labelled baculovirus.

Nanomaterials conjugated with biomacromolecules, including viruses, have great potential for in vivo applications. Therefore, it is important to evaluate the safety of nanoparticle-conjugated macromolecule biomaterials (Nano-mbio). Although a number of studies have assessed the risks of nanoparticles and macromolecule biomaterials in living bodies, only a few of them investigated Nano-mbios. Here we evaluated the in vivo safety profile of a quantum dot-conjugated baculovirus (Bq), a promising new Nano-mbio, in mice. Each animal was injected twice intraperitoneally with 50 µg virus protein labelled with around 3*10(-5)nmol conjugated qds. Control animals were injected with PBS, quantum dots, baculovirus, or a mixture of quantum dots and baculovirus. Blood, tissues and body weight were analysed at a series of time points following both the first and the second injections. It turned out that the appearance and behaviour of the mice injected with Bq were similar to those injected with baculovirus alone. However, combination of baculovirus and quantum dot (conjugated or simply mixed) significantly induced stronger adaptive immune responses, and lead to a faster accumulation and longer existence of Cd in the kidneys. Thus, despite the fact that both quantum dot and baculovirus have been claimed to be safe in vivo, applications of Bq in vivo should be cautious. To our knowledge, this is the first study examining the interaction between a nanoparticle-conjugated virus and a living body from a safety perspective, providing a basis for in vivo application of other Nano-mbios.

Effects of Maternal Exposure to Cadmium Oxide Nanoparticles During Pregnancy on Maternal and Offspring Kidney Injury Markers Using a Murine Model.

Nanoparticles (NP) are pervasive in many areas of modern life, with little known about their potential toxicities. One commercially important NP is cadmium oxide (CdO), which is used to synthesize other Cd-containing NP, such as quantum dots. Cadmium (Cd) is a well-known nephrotoxicant, but the nephrotoxic potential of CdO NP remains unknown, particularly when exposure occurs during pregnancy. Therefore, pregnant CD-1 mice were used to examine the effects of inhaled CdO NP (230 µg CdO NP/m(3)) on maternal and neonatal renal function by examining urinary creatinine and urinary biomarkers of kidney injury, including kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Inhalation of CdO NP by dams produced a fivefold increase in urinary Kim-1 with no marked effect on urinary creatinine levels. Kim-1 mRNA expression peaked by gestational day (GD) 10.5, and NGAL expression increased from GD 10.5 to 17.5. In addition, histological analyses revealed proximal tubular pathology at GD 10.5. Neonatal Kim-1 mRNA expression rose between postnatal days (PND) 7 and 14, with mammary glands/milk being the apparent source of Cd for offspring. These studies demonstrate that, similar to what is seen with other Cd forms, Cd associated with inhaled CdO NP results in renal injury to both directly exposed dam and offspring. As commercial uses for nanotechnology continue to expand throughout the world, risks for unintentional exposure in the workplace increase. Given the large number of women in the industrial workforce, care needs to be taken to protect these already vulnerable populations.

Selective inhibition of liver cancer growth realized by the intrinsic toxicity of a quantum dot-lipid complex.

Using the intrinsic toxicity of nanomaterials for anticancer therapy is an emerging concept. In this work, we discovered that CdTe/CdS quantum dots, when coated with lipids (QD-LC) instead of popular liposomes, polymers, or dendrimers, demonstrated extraordinarily high specificity for cancer cells, which was due to the difference in the macropinocytosis uptake pathways of QD-LC between the cancer cells and the normal cells. QD-LC-induced HepG2 cell apoptosis was concomitant with the activation of the JNK/caspase-3 signaling pathway. Moreover, QD-LC treatment resulted in a delay in the latent period for microtumor formation of mouse hepatocarcinoma H22 cells and inhibited tumor growth, with a reduction of 53.2% in tumor volume without toxicity in major organs after intratumoral administrations to tumor-bearing mice. Our results demonstrate that QD-LC could be a very promising theranostic agent against liver cancer.

Specific intracellular uptake of herceptin-conjugated CdSe/ZnS quantum dots into breast cancer cells.

Herceptin, a typical monoclonal antibody, was immobilized on the surface of CdSe/ZnS core-shell quantum dots (QDs) to enhance their specific interactions with breast cancer cells (SK-BR3). The mean size of the core-shell quantum dots (28 nm), as determined by dynamic light scattering, increased to 86 nm after herceptin immobilization. The in vitro cell culture experiment showed that the keratin forming cancer cells (KB) proliferated well in the presence of herceptin-conjugated QDs (QD-Her, 5 nmol/mL), whereas most of the breast cancer cells (SK-BR3) had died. To clarify the mechanism of cell death, the interaction of SK-BR3 cells with QD-Her was examined by confocal laser scanning microscopy. As a result, the QD-Her bound specifically to the membrane of SK-BR3, which became almost saturated after 6 hours incubation. This suggests that the growth signal of breast cancer cells is inhibited completely by the specific binding of herceptin to the Her-2 receptor of SK-BR3 membrane, resulting in cell death.

Self-illuminating 64Cu-doped CdSe/ZnS nanocrystals for in vivo tumor imaging.

Construction of self-illuminating semiconducting nanocrystals, also called quantum dots (QDs), has attracted much attention recently due to their potential as highly sensitive optical probes for biological imaging applications. Here we prepared a self-illuminating QD system by doping positron-emitting radionuclide (64)Cu into CdSe/ZnS core/shell QDs via a cation-exchange reaction. The (64)Cu-doped CdSe/ZnS QDs exhibit efficient Cerenkov resonance energy transfer (CRET). The signal of (64)Cu can accurately reflect the biodistribution of the QDs during circulation with no dissociation of (64)Cu from the nanoparticles. We also explored this system for in vivo tumor imaging. This nanoprobe showed high tumor-targeting ability in a U87MG glioblastoma xenograft model (12.7% ID/g at 17 h time point) and feasibility for in vivo luminescence imaging of tumor in the absence of excitation light. The availability of these self-illuminating integrated QDs provides an accurate and convenient tool for in vivo tumor imaging and detection.

Cellular mechanisms of cadmium-induced toxicity: a review.

Cadmium is a widespread toxic pollutant of occupational and environmental concern because of its diverse toxic effects: extremely protracted biological half-life (approximately 20-30 years in humans), low rate of excretion from the body and storage predominantly in soft tissues (primarily, liver and kidneys). It is an extremely toxic element of continuing concern because environmental levels have risen steadily due to continued worldwide anthropogenic mobilization. Cadmium is absorbed in significant quantities from cigarette smoke, food, water and air contamination and is known to have numerous undesirable effects in both humans and animals. Cadmium has a diversity of toxic effects including nephrotoxicity, carcinogenicity, teratogenicity and endocrine and reproductive toxicities. At the cellular level, cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Most important seems to be cadmium interaction with DNA repair mechanism, generation of reactive oxygen species and induction of apoptosis. In this article, we have reviewed recent developments and findings on cadmium toxicology.

Nanotoxicology using the sea anemone Nematostella vectensis: from developmental toxicity to genotoxicology.

Concomitant with the fast-growing advances in the synthesis and engineering of colloidal nanocrystals, an urgent evaluation of their toxicity on human beings and environment is strongly encouraged by public health organisations. Despite the in vitro approaches employed for toxicological screening of hazardous compounds, the use of simple and cost-effective living organisms may enormously contribute to solve unanswered questions related to embryotoxic and teratogenic effects of nanomaterials. Here, the sea anemone Nematostella vectensis (Cnidaria, Anthozoa) is presented as a novel model organism to profile bio/non-bio interactions and to show a comprehensive toxicological analysis performed on embryos, larvae and adults treated with fluorescent cadmium-based nanocrystals. Spanning from in vivo biodistribution to molecular investigations, different behaviours and effects depending on the composition and surface coatings are showed. Rod-shaped cadmium selenide/cadmium sulfide (CdSe/CdS) nanocrystals resulted in excellent imaging probes to track N. vectensis development with negligible adverse effects, while spherical CdTe nanocrystals severely impaired embryogenesis, resulting in aberrant phenotypes and deregulation of developmental genes, which raise severe worries for a safe use of this type of nanoparticles for human purposes and environmental contamination.

Cellular uptake, elimination and toxicity of CdSe/ZnS quantum dots in HepG2 cells.

In this work, the cellular uptake, elimination and toxicity of CdSe/ZnS QDs in HepG2 cells were comprehensively studied using inductively coupled plasma mass spectrometry (ICP-MS), MTT assay, AO/EB staining, and glutathione level and gene expression analysis. ICP-MS analytical results showed that the uptake efficiency of CdSe QDs by HepG2 cells was lower than that of Cd(II) and Se(IV), and the uptake was dose- and time-dependent. The uptake amount was related to the physicochemical properties of QDs, and NH2-QDs with smaller size were more easily taken up by cells. In combination with various biochemical methodologies, a systematic and thorough quantitative analysis of the in vitro effects of CdSe/ZnS QDs with different coatings was conducted, along with that of Cd (II) and Se (IV). Although Cd(II) above 8.9 µM exhibited obvious toxicity to the cells, no obvious toxicity of four CdSe/ZnS QDs was observed within the tested concentration range (10-100 nM), most likely due to the protection of the ZnS shell and the PEG coating. From the molecular level's point of view, QDs at concentration of 100 nM exhibit obvious impact on the cells, such as increased gene expression (MT1A and CYP1A1), which was positively correlated with the intracellular concentration of QDs.