Systematic toxicity assessment of CdTe quantum dots in Drosophila melanogaster.

The risk assessment of cadmium (Cd)-based quantum dots (QDs) used for biomedical nanotechnology applications has stern toxicity concerns. Despite cytotoxicity studies of cadmium telluride (CdTe) QDs, the systematic in vivo study focusing on its organismal effects are more relevant to public health. Therefore, the present study aims to investigate the effect of chemically synthesized 3-mercapto propionic acid-functionalized CdTe QDs on organisms' survival, development, reproduction, and behaviour using Drosophila melanogaster as a model. The sub-cellular impact on the larval gut was also evaluated. First/third instar larvae or the adult Drosophila were exposed orally to green fluorescence emitting CdTe QDs (0.2-100 µM), and organisms' longevity, emergence, reproductive performance, locomotion, and reactive oxygen species (ROS), and cell death were assessed. Uptake of semiconductor CdTe QDs was observed as green fluorescence in the gut. A significant decline in percentage survivability up to 80% was evident at high CdTe QDs concentrations (25 and 100 µM). The developmental toxicity was marked by delayed and reduced fly emergence after CdTe exposure. The teratogenic effect was evident with significant wing deformities at 25 and 100 µM concentrations. However, at the reproductive level, adult flies' fecundity, fertility, and hatchability were highly affected even at low concentrations (1 µM). Surprisingly, the climbing ability of Drosophila was unaffected at any of the used CdTe QDs concentrations. In addition to organismal toxicity, the ROS level and cell death were elevated in gut cells, confirming the sub-cellular toxicity of CdTe QDs. Furthermore, we observed a significant rescue in CdTe QDs-associated developmental, reproductive, and survival adversities when organisms were co-exposed with N-acetyl-cysteine (NAC, an antioxidant) and CdTe QDs. Overall, our findings indicate that the environmental release of aqueously dispersible CdTe QDs raises a long-lasting health concern on the development, reproduction, and survivability of an organism.

The minimum inhibitory concentration (MIC) assay with Escherichia coli: An early tier in the environmental hazard assessment of nanomaterials?

There are now over a thousand nano-containing products on the market and the antibacterial properties of some nanomaterials has created interest in their use as cleaning agents, biocides and disinfectants. Engineered nanomaterials (ENMs) are being released into the environment and this raises concerns about their effects on microbes in the receiving ecosystems. This study evaluated the bacterial toxicity of a wide range of nanomaterials with different surface coatings on Escherichia coli K-12 MG1655. The minimum inhibitory concentration (MIC) assay, which quantifies the threshold for growth inhibition in suspensions of bacteria, was used to rank the toxicity of silver (Ag), cupric oxide (CuO), cadmium telluride (CdTe) quantum dots, titanium dioxide (TiO2), nanodiamonds and multi-walled carbon nanotubes (MWCNTs). Bacteria were exposed for 12 h at 37 °C to a dilution series of the test suspensions in 96-well plates. The precision and accuracy of the method was good with coefficients of variation < 10%. In terms of the measured MIC values, the toxicity order of the ENMs was as follows: CdTe quantum dots ammonium-coated, 6 mg L-1 > Ag nanoparticles, 12 mg L-1 > CdTe quantum dots carboxylate-coated, 25 mg L-1 > CdTe quantum dots polyethylene glycol-coated, 100 mg L-1. The MIC values were above the highest test concentration used (100 mg L-1) for CuO, TiO2, nanodiamonds and MWCNTs, indicating low toxicity. The MIC assay can be a useful tool for the initial steps of ENMs hazard assessment.

Evaluation of the Content of Antimony, Arsenic, Bismuth, Selenium, Tellurium and Their Inorganic Forms in Commercially Baby Foods.

Baby foods, from the Spanish market and prepared from meat, fish, vegetables, cereals, legumes, and fruits, were analyzed to obtain the concentration of antimony (Sb), arsenic (As), bismuth (Bi), and tellurium (Te) as toxic elements and selenium (Se) as essential element. An analytical procedure was employed based on atomic fluorescence spectroscopy which allowed to obtain accurate data at low levels of concentration. Values of 14 commercial samples, expressed in nanograms per gram fresh weight, ranged for Sb 0.66-6.9, As 4.5-242, Te 1.35-2.94, Bi 2.18-4.79, and Se 5.4-109. Additionally, speciation studies were performed based on data from a non-chromatographic screening method. It was concluded that tellurium and bismuth were mainly present as inorganic forms and selenium as organic form, and antimony and arsenic species depend on the ingredients of each baby food. Risk assessment considerations were made by comparing dietary intake of the aforementioned elements through the consumption of one baby food portion a day and recommended or tolerable guideline values.

A 3D co-culture microtissue model of the human placenta for nanotoxicity assessment.

There is increasing evidence that certain nanoparticles (NPs) can overcome the placental barrier, raising concerns on potential adverse effects on the growing fetus. But even in the absence of placental transfer, NPs may pose a risk to proper fetal development if they interfere with the viability and functionality of the placental tissue. The effects of NPs on the human placenta are not well studied or understood, and predictive in vitro placenta models to achieve mechanistic insights on NP-placenta interactions are essentially lacking. Using the scaffold-free hanging drop technology, we developed a well-organized and highly reproducible 3D co-culture microtissue (MT) model consisting of a core of placental fibroblasts surrounded by a trophoblast cell layer, which resembles the structure of the in vivo placental tissue. We could show that secretion levels of human chorionic gonadotropin (hCG) were significantly higher in 3D than in 2D cell cultures, which indicates an enhanced differentiation of trophoblasts grown on 3D MTs. NP toxicity assessment revealed that cadmium telluride (CdTe) and copper oxide (CuO) NPs but not titanium dioxide (TiO2) NPs decreased MT viability and reduced the release of hCG. NP acute toxicity was significantly reduced in 3D co-culture MTs compared to 2D monocultures. Taken together, 3D placental MTs provide a new and promising model for the fast generation of tissue-relevant acute NP toxicity data, which are indispensable for the safe development of NPs for industrial, commercial and medical applications.

Cytotoxicity assessment of functionalized CdSe, CdTe and InP quantum dots in two human cancer cell models.

The toxicity of quantum dots (QDs) has been extensively studied over the past decade. Some common factors that originate the QD toxicity include releasing of heavy metal ions from degraded QDs and the generation of reactive oxygen species on the QD surface. In addition to these factors, we should also carefully examine other potential QD toxicity causes that will play crucial roles in impacting the overall biological system. In this contribution, we have performed cytotoxicity assessment of four types of QD formulations in two different human cancer cell models. The four types of QD formulations, namely, mercaptopropionic acid modified CdSe/CdS/ZnS QDs (CdSe-MPA), PEGylated phospholipid encapsulated CdSe/CdS/ZnS QDs (CdSe-Phos), PEGylated phospholipid encapsulated InP/ZnS QDs (InP-Phos) and Pluronic F127 encapsulated CdTe/ZnS QDs (CdTe-F127), are representatives for the commonly used QD formulations in biomedical applications. Both the core materials and the surface modifications have been taken into consideration as the key factors for the cytotoxicity assessment. Through side-by-side comparison and careful evaluations, we have found that the toxicity of QDs does not solely depend on a single factor in initiating the toxicity in biological system but rather it depends on a combination of elements from the particle formulations. More importantly, our toxicity assessment shows different cytotoxicity trend for all the prepared formulations tested on gastric adenocarcinoma (BGC-823) and neuroblastoma (SH-SY5Y) cell lines. We have further proposed that the cellular uptake of these nanocrystals plays an important role in determining the final faith of the toxicity impact of the formulation. The result here suggests that the toxicity of QDs is rather complex and it cannot be generalized under a few assumptions reported previously. We suggest that one have to evaluate the QD toxicity on a case to case basis and this indicates that standard procedures and comprehensive protocols are urgently needed to be developed and employed for fully assessing and understanding the origins of the toxicity arising from different QD formulations.

Toxicity assessment of repeated intravenous injections of arginine-glycine-aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice.

BACKGROUND: Nanotechnology-based near-infrared quantum dots (NIR QDs) have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine-glycine-aspartic acid (RGD) sequence (NIR QDs-RGD) can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo. MATERIALS AND METHODS: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800) to the RGD peptide (QD800-RGD). QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection). Phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils) and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen). The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including superoxide dismutase, glutathione, and malondialdehyde. The organs were also examined histopathologically. RESULTS: After one or two intravenous injections of QD800-RGD, as compared with control, no significant differences were observed in the complete blood count; biochemical indicators of blood serum, organ coefficient, and oxidation and antioxidation indicators; and no cell necrosis or inflammation were seen in the liver, spleen, kidney, or lung through histopathological examination. CONCLUSION: Our data demonstrate that the single and repeated intravenous injection of QD800-RGD at a dose needed for successful tumor imaging in vivo is not toxic to mice. Our work lays a solid foundation for further biomedical applications of NIR QDs-RGD.

Toxicity assessment of zebrafish following exposure to CdTe QDs.

CdTe quantum dots (QDs) are nanocrystals of unique composition and properties that have found many new commercial applications; therefore, their potential toxicity to aquatic organisms has become a hot research topic. The lab study was performed to determine the developmental and behavioral toxicities to zebrafish under continuous exposure to low concentrations of CdTe QDs (1-400 nM) coated with thioglycolic acid (TGA). The results show: (1) the 120 h LC(50) of 185.9 nM, (2) the lower hatch rate and body length, more malformations, and less heart beat and swimming speed of the exposed zebrafish, (3) the brief burst and a higher basal swimming rate of the exposed zebrafish larvae during a rapid transition from light-to-dark, and (4) the vascular hyperplasia, vascular bifurcation, vascular crossing and turbulence of the exposed FLI-1 transgenic zebrafish larvae.

Assessment of nanomaterial cytotoxicity with SOLiD sequencing-based microRNA expression profiling.

The cytotoxicity of nanomaterials has become a major concern in the field of nanotechnology. The key challenge is the lack of reliable methods to examine the overall cellular effects of nanomaterials. Here, a new method is developed to assess the cytological effects of nanomaterial basing on miRNA expression profiling. The SOLiD sequencing is used to acquire the miRNAs expression profiling in NIH/3T3 cells after exposure to Fe(2)O(3) NPs, CdTe QDs and MW-CNTs, respectively. The systematic analysis of miRNAs expression profiling is established by taking account of all miRNAs into their regulatory networks. By affecting the output of targeted mRNAs, miRNAs widely regulated the KEGG pathways and GO biological processes in nanomaterial treated cells. Therefore, the miRNA expression profiling can well reflect the characteristic of nanomaterials, and the method not only provide more evidences to assess biocompatibility of nanomaterials and but also clues to discover new biological effects of nanomaterials.

Teratogenicity of tellurium dioxide: prenatal assessment.

The effects of multiple maternal subcutaneous injections of tellurium dioxide (TeO2) suspended in olive oil (0-1,000 mumol/kg) from day 15 to day 19 of gestation were evaluated in the Wistar rat. External and internal soft-tissue examinations were performed on day 20 fetuses. Multiple maternal injections, at doses higher than 10 mumol/kg, resulted in a dose-related appearance of hydrocephalus, edema, exophthalmia, ocular hemorrhage, umbilical hernia, undescended testis, and small kidneys in fetuses on day 20 of gestation. At 500 mumol/kg, reduction in maternal weight gain was also observed. At this level, the incidence of the above anomalies was 100%. The 100 mumol/kg dose of Te, which did not produce apparent maternal toxic responses, resulted in a 100% incidence of hydrocephalus and edema but no fetal mortality. Thus, tellurium can be teratogenic to the rat fetus without concomitant maternal toxicity. Also, the fetal period may be more sensitive than the organogenic period for the induction of hydrocephalus. Such evidence is consistent with the development of the choroid plexus and an effect of TeO2 on the production/resorption of cerebrospinal fluid.