Cadmium nitrate and DNA methylation in gastropods: comparison between ovotestis and hepatopancreas.

Dietary ingestion is the main route of exposure to hazardous contaminants in land animals. Cadmium, a high-profile toxic metal, affects living systems at different organismal levels, including major storage organs (liver, kidneys), key organs for species survival (gonads), and epigenetic networks regulating gene expression. 5-methylcytosine (5mC) is the most common and best-characterized epigenetic mark among different modified nucleosides in DNA. This important player in methylation-driven gene expression is impacted by cadmium in sentinel terrestrial vertebrates. However, limited information exists regarding its impact on macroinvertebrates, especially land snails commonly used as (eco)toxicological models. We first investigate the methylomic effects of dietary cadmium given as cadmium nitrate on terrestrial mollusks. Mature specimens of the common brown garden snail, Cornu aspersum, were continuously exposed for four weeks to environmentally-relevant cadmium levels. We determined global genomic DNA methylation in hepatopancreas and ovotestis, as well as changes in the methylation status of CG pairs at the 5' region close to the transcription site of gene encoding the Cd-selective metallothionein (Cd-MT). Weight gain/loss, hypometabolism tendency, and survival rates were also assessed. Although this exposure event did not adversely affect survival, gastropods exposed to the highest Cd dose revealed a significant reduction in body weight and a significant increase in hypometabolic behavior. The hepatopancreas, but not the ovotestis, displayed significant hypermethylation, but only for the aforementioned specimens. We also found that the 5' end of the Cd-MT gene was unmethylated in both organs and its methylation status was insensitive to cadmium exposure. Our results are important since they provide scientists, for the first time, with quantitative data on DNA methylation in gastropod ovotestis and refine our understanding of Cd epigenetic effects on terrestrial mollusks.

A novel insight into mechanism of derangement of coagulation balance: interactions of quantum dots with coagulation-related proteins.

BACKGROUND: Quantum dots (QDs) have gained increased attention for their extensive biomedical and electronic products applications. Due to the high priority of QDs in contacting the circulatory system, understanding the hemocompatibility of QDs is one of the most important aspects for their biosafety evaluation. Thus far, the effect of QDs on coagulation balance haven't been fully understood, and limited studies also have yet elucidated the potential mechanism from the perspective of interaction of QDs with coagulation-related proteins. RESULTS: QDs induced the derangement of coagulation balance by prolonging the activated partial thromboplastin time and prothrombin time as well as changing the expression levels of coagulation and fibrinolytic factors. The contact of QDs with PTM (prothrombin), PLG (plasminogen) and FIB (fibrinogen) which are primary coagulation-related proteins in the coagulation and fibrinolysis systems formed QDs-protein conjugates through hydrogen-bonding and hydrophobic interaction. The affinity of proteins with QDs followed the order of PTM > PLG > FIB, and was larger with CdTe/ZnS QDs than CdTe QDs. Binding with QDs not only induced static fluorescence quenching of PTM, PLG and FIB, but also altered their conformational structures. The binding of QDs to the active sites of PTM, PLG and FIB may promote the activation of proteins, thus interfering the hemostasis and fibrinolysis processes. CONCLUSIONS: The interactions of QDs with PTM, PLG and FIB may be key contributors for interference of coagulation balance, that is helpful to achieve a reliable and comprehensive evaluation on the potential biological influence of QDs from the molecular level.

[Effect of exogenous CdS nanoparticle on the growth of Escherichia coli].

Semiconductor nanoparticles generate photoelectrons and photo-induced holes under light excitation, and thus may influence the growth of microbial cells. The highly oxidative holes may severely damage the cells, while the photoelectrons may promote microbial metabolism. In this study, we evaluated the effect of exogenous cadmium sulfide (CdS) nanoparticles on bacterial growth using OD600 and colony forming unit (CFU) as indicators. The oxidase activities, the concentration of pyruvate and malondialdehyde, and the expression of relevant genes assessed by real-time fluorescent quantitative PCR were analyzed to investigate the effect of excited CdS on cellular metabolism. The results showed that the OD600 and pyruvate accumulation of E. coli increased by 32.4% and 34.6%, respectively, under light conditions. Moreover, the relative expression level of the division protein gene ftsZ was increased more than 50%, and the tricarboxylic acid cycle pathway gene icdA and gltA increased by 86% and 103%, respectively. The results indicated that photoelectrons could be used by microorganisms, resulting in promoted growth and metabolism. This study gives a deep insight into the interaction between nanoparticles and bacteria.

Effect of exogenous CdS nanoparticle on the growth of Escherichia coli / 生物工程学报

Semiconductor nanoparticles generate photoelectrons and photo-induced holes under light excitation, and thus may influence the growth of microbial cells. The highly oxidative holes may severely damage the cells, while the photoelectrons may promote microbial metabolism. In this study, we evaluated the effect of exogenous cadmium sulfide (CdS) nanoparticles on bacterial growth using OD600 and colony forming unit (CFU) as indicators. The oxidase activities, the concentration of pyruvate and malondialdehyde, and the expression of relevant genes assessed by real-time fluorescent quantitative PCR were analyzed to investigate the effect of excited CdS on cellular metabolism. The results showed that the OD600 and pyruvate accumulation of E. coli increased by 32.4% and 34.6%, respectively, under light conditions. Moreover, the relative expression level of the division protein gene ftsZ was increased more than 50%, and the tricarboxylic acid cycle pathway gene icdA and gltA increased by 86% and 103%, respectively. The results indicated that photoelectrons could be used by microorganisms, resulting in promoted growth and metabolism. This study gives a deep insight into the interaction between nanoparticles and bacteria.

Hitchhiking Nanoparticles: Mesenchymal Stem Cell-Mediated Delivery of Theranostic Nanoparticles.

Nanotechnology has emerged as a promising solution to permanent elimination of cancer. However, nanoparticles themselves lack specificity to tumors. Due to enhanced migration to tumors, mesenchymal stem cells (MSCs) were suggested as cell-mediated delivery vehicles of nanoparticles. In this study, we have constructed a complex composed of photoluminescent quantum dots (QDs) and a photosensitizer chlorin e6 (Ce6) to obtain multifunctional nanoparticles, combining cancer diagnostic and therapeutic properties. QDs serve as energy donors-excited QDs transfer energy to the attached Ce6 via Förster resonance energy transfer, which in turn generates reactive oxygen species. Here, the physicochemical properties of the QD-Ce6 complex and singlet oxygen generation were measured, and the stability in protein-rich media was evaluated, showing that the complex remains the most stable in protein-free medium. In vitro studies on MSC and cancer cell response to the QD-Ce6 complex revealed the complex-loaded MSCs' potential to transport theranostic nanoparticles and induce cancer cell death. In vivo studies proved the therapeutic efficacy, as the survival of tumor-bearing mice was statistically significantly increased, while tumor progression and metastases were slowed down.

Surface-Modified Colloid CdTe/CdS Quantum Dots by a Biocompatible Thiazolidine Derivative as Promising Platform for Immobilization of Glucose Oxidase: Application to Fluorescence Sensing of Glucose.

This work focuses on the synthesis of novel modified core-shell CdTe/CdS quantum dots (QDs) and develops as a fluorescence sensor for glucose determination. The (E)-2,2'-(4,4'-dioxo-2,2'-dithioxo-2H,2'H-[5,5'-bithiazolylidene]-3,3'(4H,4'H)-diyl)bis(3- mercaptopropanoic acid) (DTM) as a new derivative of thiazolidine was synthesized and characterized and used to surface-modification of CdTe/CdS QDs. DTM-capped CdTe/CdS QDs used to immobilization of glucose oxidase (GOD). The intensity fluorescence emission of the CdSe/CdS-DTM/GOD is highly sensitive to the concentration of H2O2 as a byproduct of the catalytic oxidation of glucose. The experimental results showed that the quenched fluorescence was proportional to the glucose concentration within the range of 10 nM-0.32 µM under optimized experimental conditions. The limit of detection of this system was found to be 4.3 nM. Compared with most of the existing methods, this newly developed system possesses many advantages, including simplicity, low cost, and good sensitivity.

In vitro toxicity assessment of fungal-synthesized cadmium sulfide quantum dots using bacteria and seed germination models.

There is currently controversy over the use of quantum dots (QDs) in biological applications due to their toxic effects. Therefore, the purpose of the present study was to evaluate the toxic effect of chemical and biogenic (synthesized by Fusarium oxysporum f. sp. lycopersici) cadmium sulfide quantum dots (CdSQDs) using a bacterial model of Escherichia coli and sprouts of Lactuca sativa L. with the aim to foresee its use in the near future in biological systems. Physicochemical properties of both types of CdSQDs were determined by TEM, XRD, zeta potential and fluorescence spectroscopy. Both biogenic and chemical CdSQDs showed agglomerates of spherical CdSQDs with diameters of 4.14 nm and 3.2 nm, respectively. The fluorescence analysis showed a band around 361 nm in both CdSQDs, the zeta potential was -1.81 mV for the biogenic CdSQDs and -5.85 mv for the chemical CdSQDs. Results showed that chemical CdSQDs, presented inhibition in the proliferation of E. coli cell in a dose-dependent manner, unlike biogenic CdSQDs, that only at its highest concentration showed an antibacterial activity. Also, it was observed that after incubation with chemical and biogenic CdSQDs of L. sativa L. seeds, only the biogenic CdSQDs showed no inhibition on seed germination. In summary, our results suggest that the production route has a significant effect on the toxicity of QDs; in addition, it seems that the biological coating of the CdSQDs from F. oxysporum f. sp. lycopersici inhibit their toxic effect on bacterial strains and plant seeds.

Acetogenic bacteria utilize light-driven electrons as an energy source for autotrophic growth.

Acetogenic bacteria use cellular redox energy to convert CO2 to acetate using the Wood-Ljungdahl (WL) pathway. Such redox energy can be derived from electrons generated from H2 as well as from inorganic materials, such as photoresponsive semiconductors. We have developed a nanoparticle-microbe hybrid system in which chemically synthesized cadmium sulfide nanoparticles (CdS-NPs) are displayed on the cell surface of the industrial acetogen Clostridium autoethanogenum The hybrid system converts CO2 into acetate without the need for additional energy sources, such as H2, and uses only light-induced electrons from CdS-NPs. To elucidate the underlying mechanism by which C. autoethanogenum uses electrons generated from external energy sources to reduce CO2, we performed transcriptional analysis. Our results indicate that genes encoding the metal ion or flavin-binding proteins were highly up-regulated under CdS-driven autotrophic conditions along with the activation of genes associated with the WL pathway and energy conservation system. Furthermore, the addition of these cofactors increased the CO2 fixation rate under light-exposure conditions. Our results demonstrate the potential to improve the efficiency of artificial photosynthesis systems based on acetogenic bacteria integrated with photoresponsive nanoparticles.

Enhanced Light-Driven Hydrogen Production by Self-Photosensitized Biohybrid Systems.

Storage of solar energy as hydrogen provides a platform towards decarbonizing our economy. One emerging strategy for the production of solar fuels is to use photocatalytic biohybrid systems that combine the high catalytic activity of non-photosynthetic microorganisms with the high light-harvesting efficiency of metal semiconductor nanoparticles. However, few such systems have been tested for H2 production. We investigated light-driven H2 production by three novel organisms, Desulfovibrio desulfuricans, Citrobacter freundii, and Shewanella oneidensis, self-photosensitized with cadmium sulfide nanoparticles, and compared their performance to Escherichia coli. All biohybrid systems produced H2 from light, with D. desulfuricans-CdS demonstrating the best activity overall and outperforming the other microbial systems even in the absence of a mediator. With this system, H2 was continuously produced for more than 10 days with a specific rate of 36 µmol gdcw-1 h-1 . High apparent quantum yields of 23 % and 4 % were obtained, with and without methyl viologen, respectively, exceeding values previously reported.

Formation of cadmium sulfide nanoparticles mediates cadmium resistance and light utilization of the deep-sea bacterium Idiomarina sp. OT37-5b.

Heavy metal is one of the major factors threatening the survival of microorganisms. Here, a deep-sea bacterium designated Idiomarina sp. OT37-5b possessing strong cadmium (Cd) tolerance was isolated from a typical hydrothermal vent. Both the Cd-resistance and removal efficiency of Idiomarina sp. OT37-5b were significantly promoted by the supplement of cysteine and meanwhile large amount of CdS nanoparticles were observed. Production of H2 S from cysteine catalysed by methionine gamma-lyase was further demonstrated to contribute to the formation of CdS nanoparticles. Proteomic results showed the addition of cysteine effectively enhanced the efflux of Cd, improved the activities of reactive oxygen species scavenging enzymes, and thereby boosted the nitrogen reduction and energy production of Idiomarina sp. OT37-5b. Notably, the existence of CdS nanoparticles obviously promoted the growth of Idiomarina sp. OT37-5b when exposed to light, indicating this bacterium might grab light energy through CdS nanoparticles. Proteomic analysis revealed the expression levels of essential components for light utilization including electron transport, cytochrome complex and F-type ATPase were significantly up-regulated, which strongly suggested the formation of CdS nanoparticles promoted light utilization and energy production. Our results provide a good model to investigate the uncovered mechanisms of self-photosensitization of nonphotosynthetic bacteria for light-to-chemical production in the deep biosphere.

Defining Intermediates of Nitrogenase MoFe Protein during N2 Reduction under Photochemical Electron Delivery from CdS Quantum Dots.

Coupling the nitrogenase MoFe protein to light-harvesting semiconductor nanomaterials replaces the natural electron transfer complex of Fe protein and ATP and provides low-potential photoexcited electrons for photocatalytic N2 reduction. A central question is how direct photochemical electron delivery from nanocrystals to MoFe protein is able to support the multielectron ammonia production reaction. In this study, low photon flux conditions were used to identify the initial reaction intermediates of CdS quantum dot (QD):MoFe protein nitrogenase complexes under photochemical activation using EPR. Illumination of CdS QD:MoFe protein complexes led to redox changes in the MoFe protein active site FeMo-co observed as the gradual decline in the E0 resting state intensity that was accompanied by an increase in the intensity of a new "geff = 4.5" EPR signal. The magnetic properties of the geff = 4.5 signal support assignment as a reduced S = 3/2 state, and reaction modeling was used to define it as a two-electron-reduced "E2" intermediate. Use of a MoFe protein variant, ß-188Cys, which poises the P cluster in the oxidized P+ state, demonstrated that the P cluster can function as a site of photoexcited electron delivery from CdS to MoFe protein. Overall, the results establish the initial steps for how photoexcited CdS delivers electrons into the MoFe protein during reduction of N2 to ammonia and the role of electron flux in the photochemical reaction cycle.

Photo-biohydrogen Production by Photosensitization with Biologically Precipitated Cadmium Sulfide in Hydrogen-Forming Recombinant Escherichia coli.

An inorganic-biological hybrid system that integrates features of both stable and efficient semiconductors and selective and efficient enzymes is attractive for facilitating the conversion of solar energy to hydrogen. In this study, we aimed to develop a new photocatalytic hydrogen-production system based on Escherichia coli whole-cell genetically engineered as a biocatalysis for highly active hydrogen formation. The photocatalysis part was obtained by bacterial precipitation of cadmium sulfide (CdS), which is a visible-light-responsive semiconductor. The recombinant E. coli cells were sequentially subjected to CdS precipitation and heterologous [FeFe]-hydrogenase synthesis to yield a CdS@E. coli hybrid capable of light energy conversion and hydrogen formation in a single cell. The CdS@E. coli hybrid achieved photocatalytic hydrogen production with a sacrificial electron donor, thus demonstrating the feasibility of our system and expanding the current knowledge of photosensitization using a whole-cell biocatalyst with a bacterially precipitated semiconductor.

Nuclear Factor kappa B activation by Ag, Au nanoparticles, CdTe quantum dots or their binary mixtures in HepG2 cells.

INTRODUCTION AND OBJECTIVE: Nuclear factor kappa B (NF-κB) signalling pathway plays a central role in the regulation of cellular response to stress. The aim of the study was to investigate the ability of silver nanoparticles (AgNPs), gold nanoparticles (AuNPs), CdTe quantum dots (CdTeQDs) or their binary mixtures to stimulate NF-κB binding in HepG2 cells. A dual luciferase reporter system was used to investigate NF-κB binding. MATERIAL AND METHODS: Cells were transiently transfected with a firefly luciferase reporter system and Renilla luciferase expression plasmid as a transfection efficiency control. Twenty- four hours after transfection, the cells were treated with nanoparticles (10 µg/cm3 AgNPs, 10 µg/cm3 AuNPs, 3 µg/cm3 CdTeQDs) or with 10 ng/cm3 TNFα as a positive control. Six hours later, the cells were lysed and the activities of the luminescence of firefly and Renilla luciferases were measured using the Dual-Luciferase Reporter Assay System. RESULTS: AuNPs and CdTeQDs alone significantly inhibited NF-κB binding activity. Co-treatment with AgNPs and CdTeQDs resulted in an additive effect, whereas the presence of AgNPs diminished the inhibitory effect of AuNPs. Interestingly, significant antagonism was observed between AuNPs and CdTeQDs, suggesting a similar mode of action. CONCLUSIONS: Comparison of the NF-κB binding activity induced by the mixtures of NPs suggests that in some cases NF-κB binding activity might differ from that observed for the NPs alone.

Consequences of surface coatings and soil ageing on the toxicity of cadmium telluride quantum dots to the earthworm Eisenia fetida.

The bioaccumulation potential and toxic effects of engineered nanomaterials (ENMs) to earthworms are poorly understood. Two studies were conducted following OECD TG 222 on Eisenia fetida to assess the effects of CdTe QDs with different coatings and soil ageing respectively. Earthworms were exposed to carboxylate (COOH), ammonium (NH4+), or polyethylene glycol (PEG) coated CdTe QDs, or a micron scale (bulk) CdTe material, at nominal concentrations of 50, 500 and 2000 mg CdTe QD kg-1 dry weight (dw) for 28 days in Lufa 2.2 soil. In the fresh soil study, earthworms accumulated similar amounts of Cd and Te in the CdTe-bulk exposures, while the accumulation of Cd was higher than Te during the exposures to CdTe QDs. However, neither the total Cd, nor Te concentrations in the earthworms, were easily explained by the extractable metal fractions in the soil or particle dissolution. There were no effects on survival, but some retardation of growth was observed at the higher doses. Inhibition of Na+/K+-ATPase activity with disturbances to tissue electrolytes, as well as tissue Cu and Mn were observed, but without depletion of total glutathione in the fresh soil experiment. Additionally, juvenile production was the most sensitive endpoint, with estimated nominal EC50 of values >2000, 108, 65, 96 mg CdTe kg-1 for bulk, PEG-, COOH- and NH4+-coated CdTe QDs, respectively. In the aged soil study, the accumulation of Cd and Te was higher than in the fresh soil study in all CdTe QD exposures. Survival of the adult worms was reduced in the top CdTe-COOH and -NH4+ QD exposures by 55 ±â€¯5 and 60 ±â€¯25%, respectively; and with decreases in growth. The nominal EC50 values for juvenile production in the aged soil were 165, 88, 78 and 63 mg CdTe kg-1 for bulk, PEG-, COOH- and NH4+-coated CdTe QDs, respectively. In conclusion, exposure to nanoscale CdTe QDs, regardless of coating, caused more severe toxic effects that the CdTe bulk material and the toxicity increased after soil ageing. There were some coating-mediated effects, likely due to differences in the metal content and behaviour of the materials.

Escherichia coli-based synthesis of cadmium sulfide nanoparticles, characterization, antimicrobial and cytotoxicity studies.

The present research describes the synthesis of cadmium sulfide (CdS) nanoparticles from Escherichia coli under the influence of bacterial enzyme sulphate reductase and study on their cytotoxicity for applications in cancer therapy. Escherichia coli cells were used to synthesize CdS nanoparticles under different concentrations of cadmium chloride and sodium sulfide. The morphology of the nanoparticles was analysed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) was used for elemental analysis of nanoparticles. Fourier-transform infrared spectroscopy analysis (FTIR) was performed to assess the functional groups of the nanoparticles. Crystalline nature of nanoparticles was assessed using powder X-ray diffraction (XRD). Antibacterial studies of CdS nanoparticles were carried out on foodborne pathogens and cytotoxicity studies were carried out on Mus musculus skin melanoma (B16F10) and human epidermoid carcinoma (A431) cell lines. CdS nanoparticle showed more cytotoxic effect on cancer cells compared with standard 5-aminolevulinic acid (5-ALA). The Escherichia coli-synthesized CdS nanoparticles showed highest zone of inhibition in the ratio 4:1 of cadmium chloride and sodium sulfide on all tested bacterial strains. The nanoparticles were also tested for haemolytic activity on RBC cells, which exhibited lower cytotoxicity than sodium dodecyl sulphate which was used as positive control. The cytotoxicity of CdS nanoparticles assessed on A431 cells showed an inhibition of 81.53% at 100 µM concentration while the cytotoxicity assessed on B16F10 cells showed an inhibition of 75.71% at 200 µM concentration which was much efficient than 5-ALA which showed an inhibition of 31.95% at a concentration against B16F10 cells and 33.45% against A431 cells at a concentration of 1 mM. Cadmium sulfide nanoparticles were thus found to be highly toxic on cancer cells compare with standard anticancerous drug 5-ALA.

Segment-specific and direction-dependent transport of cadmium and manganese in immortalized S1, S2, and S3 cells derived from mouse kidney proximal tubules.

The kidney proximal tubule is a target of many renal toxicants, including cadmium (Cd), and also a place of reabsorption of essential metals in glomerular filtrate to systemic circulation. Although the mechanisms of metal transport in the convoluted proximal tubule (S1 and S2 segments) and the straight proximal tubule (S3 segment) may differ, little is known about the segment-specific modes of metal transport. Here, we utilized immortalized cell lines derived from the S1, S2, and S3 segments of mouse kidney proximal tubules, and examined the segment-specific and direction-dependent transport of Cd and manganese (Mn) using a trans-well culture system. The results showed that the uptakes of Cd2+ and Mn2+ from apical sides were the highest in S3 cells, and Cd2+, Mn2+, and Zn2+ mutually inhibited the apical uptake of each metal. As the expression of ZIP8, a zinc transporter having affinities for Cd2+ and Mn2+, was the highest in S3 cells, ZIP8 may contribute largely to the apical uptakes of these metals. The efficient uptake of Mn2+ from apical side of S3 cells may suggest an important role of ZIP8 in proximal tubule in reabsorption of Mn, an essential metal. Our study demonstrated that S1, S2, and S3 cells provide a useful tool for studying the segment-specific and direction-dependent transport of both toxic and essential metals in the kidney's proximal tubules.

Biosynthesized CdS nanoparticles disturb E. coli growth through reactive oxygen production.

AIMS: E. coli is a widely known model organism for life science research, especially in modern bio-engineering and industrial microbiology. The goal of our current study is to understand the growth inhibitory mechanism of biosynthesized CdS nanoparticles on E. coli bacteria. MAIN METHODS: Characterization of Aspergillus foetidus mediated CdS nanoparticles has been confirmed by Zeta potential, AFM and HRTEM analyses. Furthermore, we investigated the contribution of reactive oxygen species (ROS) and subsequently lipid peroxidation on the growth of E. coli. FACS and fluorometric studies were used to know the ROS production upon CdS nanoparticle treatment. Lipid peroxidation measurement was studied by thiobarbituric acid (TBA) assay. KEY FINDINGS: The synthesized CdS nanoparticles are roughly spherical, poly-dispersed in nature and are in ~15 nm of size. Furthermore, our investigation confirmed that the cells treated with 200 µl of CdS nanoparticles produce about 50 % more ROS and about 5 times of lipid peroxidation over control cells. In addition, the number of E. coli colony survival and cell filamentation strongly depend on such lipid peroxidation caused by ROS, which actually produced due to the interaction with biosynthesized CdS nanoparticles in growth media. SIGNIFICANCE: The current research would be helpful for the mechanistic understanding of growth inhibition of E. coli by CdS nanoparticle. This may be useful for industrial applications of E. coli like bacteria.

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.

Exploring the conformational changes in fibrinogen by forming protein corona with CdTe quantum dots and the related cytotoxicity.

This study describes synthesis of N­acetyl­l­cysteine-capped CdTe quantum dots (QDs) and investigates their interaction with plasma protein fibrinogen (FIB) and the structural changes of FIB. It is shown that the interaction of QDs with FIB is a spontaneous process and the major driving forces are van der Waals forces and hydrogen bonds. Multi-spectroscopic measurements show that the intrinsic fluorescence of FIB was quenched and secondary and tertiary structures were altered due to the interaction with QDs. In addition, the aggregation state of FIB was altered in the presence of QDs. Furthermore, the formed complexes of FIB with QDs reduced the cytotoxicity of QDs. The coating of FIB on QDs could lower intracellular QDs uptake and therefore result in less released cadmium ions and ROS productions. This study, therefore, might be helpful to the comprehensive understanding of QDs toxicity and provide evidence for assessing the safe application of nanoparticles.

Triple-Labeling of Polymer-Coated Quantum Dots and Adsorbed Proteins for Tracing their Fate in Cell Cultures.

Colloidal CdSe/ZnS quantum dots were water solubilized by overcoating with an amphiphilic polymer. Human serum albumin (HSA) as a model protein was either adsorbed or chemically linked to the surface of the polymer-coated quantum dots. As the quantum dots are intrinsically fluorescent, and as the polymer coating and the HSA were fluorescent labeled, the final nanoparticle had three differently fluorescent components: the quantum dot core, the polymer shell, and the human serum albumin corona. Cells were incubated with these hybrid nanoparticles, and after removal of non-internalized nanoparticles, exocytosis of the three components of the nanoparticles was observed individually by flow cytometry and confocal microscopy. The data indicate that HSA is partly transported with the underlying polymer-coated quantum dots into cells. Upon desorption of proteins, those initially adsorbed to the quantum dots remain longer inside cells compared to free proteins. Part of the polymer shell is released from the quantum dots by enzymatic degradation, which is on a slower time scale than protein desorption. Data are quantitatively analyzed, and experimental pitfalls, such as the impact of cell proliferation and fluorescence quenching, are discussed.