Interactions between CdTe quantum dots and plasma proteins: Kinetics, thermodynamics and molecular structure changes.

Environmental particulate matter, especially ultrafine particles (< 100 nm in diameter), can damage the endothelium and favor cardiovascular disease in the general population. With the wide application of nanomaterials, exposure to nanoscale particles (nanoparticles) in the environment is increasing. Systematic study of the interaction of nanoparticles with plasma proteins is critically important for understanding the cardiovascular toxicity of nanomaterials. We combined kinetics and thermodynamics information from surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) and conformational data from fluorescence spectroscopy and circular dichroism (CD) to explore the binding mechanism between cadmium telluride quantum dots (CdTe QDs) and plasma proteins. Special attention was paid to the interaction between CdTe QDs and coagulation-related proteins and the effects of CdTe QDs on protein conformation. The results showed that the binding affinities of CdTe QDs and plasma proteins depend on the nature of the protein and follow the order of fibrinogen (FIB)> plasminogen (PLG) > thrombin (TM) > metallothionein-II (MT-II) > human serum albumin (HSA). The interaction was primarily attributed to hydrophobic forces and the spontaneity of the occurrence of the interaction, and the protein secondary structures of FIB and PLG were changed significantly. The information gained in this study might shed light on the potential toxicity of QDs to the cardiovascular system.

Genome-wide Transcriptional Analysis of Oxidative Stress-related Genes and Pathways Induced by CdTe aqQDs in Mice.

Objective: Quantum dots (QDs) has widely applied in the field of science, whose potential toxic effect has increasingly become a focus concern we need pay attention to in public health. The purpose of this article was to explore the toxicity mechanism with oxidative damage from treatment with QDs at the molecular level through a gene microarray. Methods: Mice were administered aqueously synthesized cadmium telluride QDs (CdTe aqQDs) via intravenous tail injection of a 2 µmol/kg solution (based on the molar mass of Cd), and their kidneys were collected at 1 day in strict accordance with the programs used for treated mice. We determined the hierarchical clustering of expression ratios, enriched gene ontology (GO) terms and signaling pathways through gene microarray analysis and bioinformatics analysis in kidney tissue and screened the key enzyme genes, which were verified by real-time quantitative polymerase chain reaction (real-time qPCR). Results: Compared to control group, 459 lncRNAs (197 down-regulated and 262 up-regulated) and 256 mRNAs (103 down-regulated and 153 up-regulated) were differentially expressed. According to biological processes in enriched GO terms, the response to a redox state played a significant role in the biological processes involved altered genes. Pathway analysis showed that the signaling pathways that involved cytochrome P450 (CYP450) enzymes had a close relationship with QDs. Among these signaling pathways, gene expression profiling revealed that selected differentially expressed mRNAs (CYP19A1, CYP1B1, CYP11A1, CYP11B2, and CYP17A1 in the kidney and CYP19A1 and CYP1B1 in the liver) were validated by real-time qPCR, resulting in expression levels of CYP11A1, CYP11B2 and CYP17A1 in the kidney and CYP19A1 and CYP1B1 in the liver that were significantly increased, however in expression levels of CYP19A1 and CYP1B1 compared with control group in the kidney, there was no significant difference. Conclusions: Our results provide a foundation for and potential insight into the role of CYP450-related genes in QD-induced oxidative stress. QDs may produce a great deal of reactive oxygen species (ROS) by promoting high expression of CYP450 enzymes and accumulating steroid hormones, which may be an important toxicity mechanism for mediating oxidative stress and tissue damage.

A novel strategy to evaluate the degradation of quantum dots: identification and quantification of CdTe quantum dots and corresponding ionic species by CZE-ICP-MS.

In view of the significance and urgency of the speciation analysis of quantum dots (QDs) and their degradation products for clarifying their degradation rules and toxicity mechanisms, a method for the identification and quantification of CdTe QDs and corresponding ionic species in complex matrices was developed using capillary zone electrophoresis (CZE) coupled to inductively coupled plasma-mass spectrometry (ICP-MS). The quality assessment of commercial CdTe QDs and serum pharmacokinetics of synthesized CdTe QDs in rats were successfully undertaken using the developed CZE-ICP-MS method.

Dual signal amplification strategy for high-sensitivity detection of copper species in bio-samples with a tunable dynamic range.

A facile and sensitive method with a tunable dynamic range has been proposed for the detection of Cu2+ based on the self-cleavage of Cu2+-specific DNAzyme and the Cu2+-based inhibition of HRP activity, and this method was applied to evaluate the copper species in healthy people and WD patients.

Dose and time effect of CdTe quantum dots on antioxidant capacities of the liver and kidneys in mice.

Although quantum dot (QD)-induced toxicity occurs due to free radicals, generation of oxidative stress mediated by reactive oxygen species (ROS) formation is considered an important mechanism. However, free radical mechanisms are essentially difficult to elucidate at the molecular level because most biologically relevant free radicals are highly reactive and short-lived, making them difficult to directly detect, especially in vivo. Antioxidants play an important role in preventing or, in most cases, limiting the damage caused by ROS. Healthy people and animals possess many endogenous antioxidative substances that scavenge free radicals in vivo to maintain the redox balance and genome integrity. The antioxidant capacity of an organism is highly important but seldom studied. In this study, the dose and time effects of CdTe QDs on the antioxidant capacities of the liver and kidneys were investigated in mice using the electron paramagnetic resonance (EPR) spin-trapping technique. We found that the liver and kidneys of healthy mice contain specific antioxidant capacities that scavenge ·OH and ·O2-. Furthermore, oxidative stress markers (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], glutathione [GSH] and malondialdehyde [MDA]) were examined. In dose course studies, the free radical scavenging efficiencies of the liver and kidneys were found to gradually decrease with increasing concentration of CdTe QD exposure. The activities and levels of SOD, CAT, GPx and MDA were observed to increase in treated groups, whereas those of GSH were reduced. The time course studies revealed that the QD-induced antioxidant efficiency reduction was time dependent with GSH decrease and could recover after a period of time. These experimental results offer new information on QD toxicity in vivo. Specifically, CdTe QDs can deplete GSH to reduce the elimination ability of the liver and kidneys for ·OH and ·O2-, thus inducing oxidative damage to tissues.

Time-dependent toxicity of cadmium telluride quantum dots on liver and kidneys in mice: histopathological changes with elevated free cadmium ions and hydroxyl radicals.

A complete understanding of the toxicological behavior of quantum dots (QDs) in vivo is of great importance and a prerequisite for their application in humans. In contrast with the numerous cytotoxicity studies investigating QDs, only a few in vivo studies of QDs have been reported, and the issue remains controversial. Our study aimed to understand QD-mediated toxicity across different time points and to explore the roles of free cadmium ions (Cd(2+)) and hydroxyl radicals (·OH) in tissue damage. Male ICR mice were administered a single intravenous dose (1.5 µmol/kg) of CdTe QDs, and liver and kidney function and morphology were subsequently examined at 1, 7, 14, and 28 days. Furthermore, ·OH production in the tissue was quantified by trapping · OH with salicylic acid (SA) as 2,3-dihydroxybenzoic acid (DHBA) and detecting it using a high-performance liquid chromatography fluorescence method. We used the induction of tissue metallothionein levels and 2,3-DHBA:SA ratios as markers for elevated Cd(2+) from the degradation of QDs and ·OH generation in the tissue, respectively. Our experimental results revealed that the QD-induced histopathological changes were time-dependent with elevated Cd(2+) and ·OH, and could recover after a period of time. The Cd(2+) and ·OH exhibited delayed effects in terms of histopathological abnormalities. Histological assessments performed at multiple time points might facilitate the evaluation of the biological safety of QDs.