Toxicity Of Quantum Dots Research Articles

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

This study describes synthesis of N‑acetyl‑l‑cysteine-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.

Copper Indium Disulfide Quantum Dot Light Emitting Diodes for Display and Lighting Technologies

While significant advances in the development of quantum dot light emitting diodes (QLEDs) have been reported, these devices are primarily based on cadmium chalcogenide quantum dot (QD) materials. Both environmental and health concerns arise due to the toxicity of cadmium and consequently, alternative less toxic QDs must be developed for large scale QLED applications such as display and solid state lighting technologies. In this work, copper indium disulfide (CIS) was investigated as an alternative QD material for QLED applications. Through experimentation with material synthesis and device fabrication, this project aimed to develop high performing CIS QLEDs. Several synthetic approaches were experimented with and it was determined that the injection of shorter chain 1-octanethoil as sulfur precursor with extensive shell reaction time resulted in highly luminescent QDs. Single color QLEDs were fabricated based on typical device structure, using highly luminescent synthesized CIS QDs as the emissive layer in multilayer devices. Varying the shell reaction time of QDs in order to vary shell thickness resulted in significant differences in device performance. Using thicker shell QDs, high performing devices were obtained with the best performing QLEDs displaying a high peak current efficiency of 14.7 cd/A and high external quantum efficiency of 5.2%.

Involvement of ABC transporters in the efflux and toxicity of MPA-COOH-CdTe quantum dots in human breast cancer SK-BR-3 cells.

This paper aimed to study the possible involvement of adenosine triphosphate-binding cassette (ABC) transporters in the detoxification of quantum dots (QDs) in human breast carcinoma (SK-BR-3) cells. The effects of QD sizes on such interactions were also evaluated. For this purpose, we used monodispersed MPA-COOH-CdTe QDs with different diameters (emission length at 560 and 625 nm, named as QD-560 and QD-625). Such QDs tended to accumulate in cells and cause significant toxicity. Using specific inhibitors of ABC transporters, the cellular accumulation and toxicity of QDs in SK-BR-3 cells were significantly affected. Moreover, treatment of QDs caused concentration- and time-dependent induction of ABC transporters. Furthermore, the induction effects of smaller QDs were found to be greater than larger ones at equivalent concentrations, suggesting a size-dependent recognition of substrates by ABC transporters. Overall, these results provided important support for the modulation of QDs toxicity by ABC transporters.

Imaging of water soluble CdTe/CdS core-shell quantum dots in inhibiting multidrug resistance of cancer cells

Two different colors of water-soluble core-shell quantum dots CdTe/CdS (green and orange red) have been synthesized and characterized in this paper. The formation of core-shell quantum dots not only improves the fluorescence quantum yield, but also reduces the biological toxicity of quantum dots, and improves the fluorescence lifetime. Two novel fluorescent bioprobes, CdTe/CdS (λem = 545 nm)-5-Fu and Bio-CdTe/CdS (λem = 600 nm)-TAM, have been synthesized via the interaction of these two core-shell quantum dots with anticancer drugs (5-Fu) and P-gp inhibitors (TAM), respectively. These two fluorescent probes have been simultaneously used in fluorescence imaging of human breast cancer cells MDA-MB-231/MDR. It can be observed that under the action of P-gp inhibitors distributed on the cell membrane, anticancer drugs can be retained in cancer cells. According to the color of quantum dots on the probe, the visualization results of the action of anticancer drugs and P-gp inhibitors can be obtained. This study shows that to prepare functional bioprobes using core-shell quantum dots CdTe/CdS has great potential in the field of biomedical research such as anticancer drugs.

Cell Imaging Using Two-Photon Excited CdS Fluorescent Quantum Dots Working within the Biological Window.

In recent years, two-photon excited semiconductor quantum dots (QDs) have been the subject of intense investigation due to their long excitation wavelength which helps to achieve deeper penetration and higher image resolution in optical bioimaging. In this paper, water-soluble CdS QDs were synthesized using a hydrothermal method and applied to human liver hepatocellular carcinoma (HepG2) cells. The first-principles calculation suggested that the S-rich defected structure contributes to a narrower band gap compared to the pristine structure. The resulting fluorescence wavelength was significantly red shifted, which was attributed to the deep defect states emission. The large Stokes shifts (> 200 nm) of the QDs can eliminate the possible cross-talk between the excitation light and the emission light. Two-photon induced red fluorescence emission can avoid overlapping with the autofluorescence emission of biological samples. The uptake and cell viability measurements of the HepG2 cells showed a good biocompatibility and a low toxicity of CdS QDs. Two-photon excited scanning microscopy images revealed that the HepG2 cells incubated with CdS QDs emitted bright red upconversion fluorescence and the fluorescence brightness was 38.2 times of that of the control group. These results support CdS QDs as a good candidate for application in cellular imaging.

An Integrated Multilevel Analysis Profiling Biosafety and Toxicity Induced by Indium- and Cadmium-Based Quantum Dots in Vivo.

Indium phosphide quantum dots (QDs) have emerged as a new class of fluorescent nanocrystals for manifold applications, from biophotonics to nanomedicine. Recent efforts in improving the photoluminescence quantum yield, the chemical stability and the biocompatibility turned them into a valid alternative to well established Cd-based nanocrystals. In vitro studies provided first evidence for the lower toxicity of In-based QDs. Nonetheless, an urgent need exists for further assessment of the potential toxic effects in vivo. Here we use the freshwater polyp Hydra vulgaris, a well-established model previously adopted to assess the toxicity of CdSe/CdS nanorods and CdTe QDs. A systematic multilevel analysis was carried out in vivo, ex vivo, and in vitro comparing toxicity end points of CdSe- and InP-based QDs, passivated by ZnSe/ZnS shells and surface functionalized with penicillamine. Final results demonstrate that both the chemical composition of the QD core (InP vs CdSe) and the shell play a crucial role for final outcomes. Remarkably, in absence of in vivo alterations, cell and molecular alterations revealed hidden toxicity aspects, highlighting the biosafety of InP-based nanocrystals and outlining the importance of integrated multilevel analyses for proper QDs risk assessment.

CdSe/ZnS Quantum Dots Impaired the First Two Generations of Placenta Growth in an Animal Model, Based on the Shh Signaling Pathway.

The toxicity, especially the transgenerational toxicity of quantum dots (QDs) in vivo, is still scarcely understood in spite of great promising applications of QDs in biomedicine. In this study, the maternal status, pregnancy outcome, and fetus development of parental generation (P0) to offspring in three generations (F3) were investigated after Kunming mice perinatal (GD 13-PND 5) exposure to Cd containing QDs (CdSe/ZnS QDs) and CdCl2. The results show CdSe/ZnS QDs induced placenta injuries in P0 and diminished placenta diameters in F1 and F2. Bodyweight growth decreased in the CdSe/ZnS QDs treatment group in the F1 and F2 generation. Additionally, CdSe/ZnS QDs significantly altered the expression of key genes in the Shh signal pathway. Overall, this study exhibited that the CdSe/ZnS QDs exposure during perinatal period impaired placenta growth in the first two generations, but not on the third generation. The toxicological actions of the CdSe/ZnS QDs might be through the effects on the Shh signal pathway.

Exposure to MPA-capped CdTe quantum dots causes reproductive toxicity effects by affecting oogenesis in nematode Caenorhabditis elegans

Quantum dots (QDs), considered as a type of excellent semiconductor nanomaterial, are widely employed and have a number of important applications. However, QDs have the potential to produce adverse effects and toxicity with the underlying molecular mechanisms not well understood. Herein, Caenorhabditis elegans was used for in vivo toxicity assessment to detect the reproductive toxicity of CdTe QDs. We found that exposure to CdTe QDs particles (≥ 50 mg/L) resulted in a defect in reproductive capacity, dysfunctional proliferation and differentiation, as well as an imbalance in oogenesis by reducing the number of cells in pachytene and diakinesis. Further, we identified a SPO-11 and PCH-2 mediated toxic mechanism and a GLP-1/Notch mediated protective mechanism in response to CdTe QDs particles (≥ 50 mg/L). Taken together, these results demonstrate the potential adverse impact of CdTe QDs (≥ 50 mg/L) exposure on oogenesis and provide valuable data and guidelines for evaluation of QD biocompatibility.

Combining hydrophilic chemotherapy and hydrophobic phytotherapy via tumor-targeted albumin\u2013QDs nano-hybrids: covalent coupling and phospholipid complexation approaches

BackgroundThe rationale of this study is to combine the merits of both albumin nanoparticles and quantum dots (QDs) in improved drug tumor accumulation and strong fluorescence imaging capability into one carrier. However, premature drug release from protein nanoparticles and high toxicity of QDs due to heavy metal leakage are among challenging hurdles. Following this platform, we developed cancer nano-theranostics by coupling biocompatible albumin backbone to CdTe QDs and mannose moieties to enhance tumor targeting and reduce QDs toxicity. The chemotherapeutic water soluble drug pemetrexed (PMT) was conjugated via tumor-cleavable bond to the albumin backbone for tumor site-specific release. In combination, the herbal hydrophobic drug resveratrol (RSV) was preformulated as phospholipid complex which enabled its physical encapsulation into albumin nanoparticles.ResultsAlbumin–QDs theranostics showed enhanced cytotoxicity and internalization into breast cancer cells that could be traced by virtue of their high fluorescence quantum yield and excellent imaging capacity. In vivo, the nanocarriers demonstrated superior anti-tumor effects including reduced tumor volume, increased apoptosis, and inhibited angiogenesis in addition to non-immunogenic response. Moreover, in vivo bioimaging test demonstrated excellent tumor-specific accumulation of targeted nanocarriers via QDs-mediated fluorescence.ConclusionMannose-grafted strategy and QD-fluorescence capability were beneficial to deliver albumin nanocarriers to tumor tissues and then to release the anticancer drugs for killing cancer cells as well as enabling tumor imaging facility. Overall, we believe albumin–QDs nanoplatform could be a potential nano-theranostic for bioimaging and targeted breast cancer therapy.

Evaluation of the novel nanoparticle material – CdSe quantum dots on Chlorella pyrenoidosa and Scenedesmus obliquus: Concentration-time-dependent responses

Quantum dots (QDs), as a kind of novel nanomaterial, have the extensive applications in various fields, inevitably leading to increasing risks for the ecological environment. The mobilization of cadmium including metal smelting and subsequent machining for multifarious applications has caused the release of cadmium element into the environment. In this study, we evaluated the potential toxicity of a novel nanoparticle material CdSe QDs, using two green algae Chlorella pyrenoidosa and Scenedesmus obliquus. The impact of CdSe QDs and cadmium ions on algae and the sensitivity of the two algae on target compounds were also considered and compared. Our results showed the algal growth rates and chlorophyll content decreased with increasing exposure concentrations and durations. Moreover, the glutathione levels were decreased while the activities of superoxide dismutase increased, exhibiting their pivotal functions in defeating toxic stress. The increment of malondialdehyde levels revealed that the stresses of CdSe QDs and cadmium ions were contributed to the occurrence of oxidative damage. Our study also indicated that the impact of CdSe QDs was stronger than that of cadmium nitrate and the algal response was also species-specific. In addition, the TEM photographs of the algal ultrastructure showed the presence of surface attachment and uptake of QDs.

The effect of PEG functionalization on the in vivo behavior and toxicity of CdTe quantum dots.

CdTe quantum dots (QDs) are considered a potential toxic substance because they contain metal ions. However, most toxicology data are derived from in vitro studies or limited in vivo analysis and may not reflect in vivo responses and biodistribution. Proper modification is one of the most widely used routes to reduce the toxicity of QDs. Herein, we demonstrated the role of polyethylene glycol (PEG) in decreasing the toxicity of QDs by studying the animal survival, clinical biochemistry, organ histology, biodistribution and oxidative stress in thioglycolic acid (TGA)- and mercapto-acetohydrazide (TGH)-stabilized CdTe QD (TGA/TGH-CdTe QD)-treated groups. Via the histology, transmission electron microscopy (TEM) and biodistribution results, it was found that the QDs mainly accumulated in the liver and kidney at 7 days post-injection, and obvious tissue damage was also observed in the bare TGA/TGH-CdTe QD group. Based on the evaluation of oxidative stress in the liver and kidney, the indicators exhibited an obvious variation with a high dose of TGA/TGH-CdTe QDs. In contrast, the QD aggregation decreased in the liver and kidney with no clear physiological index variation after PEG functionalization. Thus, PEG plays an important role in decreasing the toxicity of the CdTe QDs, and both the accumulation of cadmium and oxidative stress variation instead of an isolation factor are responsible for the in vivo toxicity of these QDs.

Quantum Dots in Biomedical Applications

Semiconducting nanocrystals, more commonly known as quantum dots, possess unique size and shape dependent optoelectronic properties. In recent years, these unique properties have attracted much attention in the biomedical field to enable real-time tissue imaging (bioimaging), diagnostics, single molecule sensors, and drug delivery, among many other areas. The optical properties of quantum dots can be tuned by size and composition, and their small size and high surface area make them excellent candidates for intracellular tracking, diagnostics, in vivo imaging, and therapeutic delivery. We discuss recent advances and challenges in the molecular design of quantum dots are discussed, along with applications of quantum dots as drug delivery vehicles, theranostic agents, single molecule sensors, and real-time in vivo deep tissue imaging agents. We present a detailed discussion of the biodistribution and toxicity of quantum dots, and highlight recent advances to improve long-term stability in biological buffers, increase quantum yield following bioconjugation, and improve clearance from the body. Last, we present an outlook on future challenges and strategies to further advance translation to clinical application.

Quantum Dot Cellular Uptake and Toxicity in the Developing Brain: Implications for Use as Imaging Probes.

Nanometer-sized luminescent semiconductor quantum dots (QDs) have been utilized as imaging and therapeutic agents in a variety of disease settings, including diseases of the central nervous system. QDs have several advantages over traditional fluorescent probes including their small size (5–10 nm), tunable excitation and emission spectra, tailorable surface functionality, efficient photoluminescence, and robust photostability, which are ideal characteristics for in vivo imaging. Although QDs are promising imaging agents in brain-related applications, no systematic evaluation of QD behavior in brain-relevant conditions has yet been done. Therefore, we sought to investigate QD colloidal stability, cellular uptake, and toxicity in vitro, ex vivo, and in vivo in the brain environment. We found that QD behavior is highly dependent on surface functionality and that treatment of cultured organotypic whole hemisphere (OWH) slices with QDs results in dose-dependent toxicity and metallothionein increase, but no subsequent mRNA expression level changes in inflammatory cytokines or other oxidative stress. QDs coated with poly(ethylene glycol) (PEG) were protected from aggregation in neurophysiologically relevant fluids and in tissue, allowing for greater penetration. Importantly, QD behavior differed in cultured slices as compared to monolayer cell cultures, and behavior in cultured slices aligned more closely with that seen in vivo. Irrespective of surface chemistry and brain-relevant platform, non-aggregated QDs were primarily internalized by microglia in a region-dependent manner both in slices and in vivo upon systemic administration. This knowledge will help guide further engineering of candidate QD-based imaging probes for neurological application.

Systematic evaluation of graphene quantum dot toxicity to male mouse sexual behaviors, reproductive and offspring health

Graphene quantum dots (GQDs) have attracted considerable attention across multiple fields, particularly biomedical research. However, the effects of GQDs on reproductive and offspring health in mammals are unclear. Here, we show that GQD exposure via oral gavage or intravenous injection had no effect on the frequency and timing of sexual behaviors in male mice. GQD-exposed male mice retained healthy structural and functional reproductive physiology (e.g., production and storage of healthy sperm, maintenance of normal total protein and key enzyme concentrations in testes) of the testes and epididymides, as well as normal testosterone levels. Female mice housed with GQD-exposed males produced first, second, and subsequent litters of healthy pups without obvious differences to females housed with buffer-treated males. These findings may be explained by the low toxicity of GQDs in germ cells and their rapid excretion after exposure in mice, mainly via the urine and/or feces; GQDs, even at high doses, are virtually undetectable in male mouse testis, epididymis, and brain. Our findings reveal the short- and long-term effects of GQD exposure on male mouse sexual behaviors, reproductive activity, and offspring development and indicate the potential mechanisms of action of GQDs to provide further insight into their bio-safety.

Evaluation of toxicity and genotoxicity of nano nanoparticles Ag2S, synthesised by biological matrix, on Drosophila melanogaster Mg. (Diptera: Drosophilidae)

Aim. To evaluate the toxicity and genotoxicity of Ag2S quantum dots that had been synthesized by the mycelium of the fungus Pleurotus ostreatus on Drosophila melanogaster. Methods. The toxicity of nanoparticles was determined by assessing the survival rate of imagos and larvae. Genotoxicity was studied in the reparation test. The influence of nanoparticles on the development of the D. melanogaster reproductive system was determined by evaluating the number of ovariols. Results. The toxic effects of ionic silver and the absence of such effects in biosynthetic Ag2S nanoparticles had been shown. The negative influence of biosynthesized Ag2S nanoparticles and biomaterials and ionic silver on the development of D. melanogaster reproductive system had been revealed. There was no genotoxic effect for all investigated specimens. Conclusions. Ag2S biosynthesized quantum dots do not have a toxic and genotoxic effects on D. melanogaster at the concentration of 1.5 mg/ml. However, the action of Ag2S (salt), the biological matrix Pleurotus and biosynthetic Ag2S nanoparticles leads to a decrease in the number of ovariols.
 Keywords: Ag2S nanoparticles, D. melanogaster, toxicity, genotoxicity.

Biocompatibility and toxicity of graphene quantum dots for potential application in photodynamic therapy.

Achieving reliably high production of reactive oxygen species (ROS) in photodynamic therapy (PDT) remains challenging. Graphene quantum dots (GQDs) hold great promise for PDT. However, the photochemical processes leading to GQD-derived ROS generation have not yet been fully elucidated. Physicochemical characteristics of GQDs were comprehensively investigated, including electron paramagnetic resonance analysis of singlet oxygen production. Dark toxicity was assessed in vitro and in vivo. GQDs demonstrated excellent photoluminescent features, corrosion resistance, high water solubility, high photo/pH-stability, in vitro and in vivo biocompatibility and very efficient singlet oxygen/ROS generation. The enhanced ROS generation, combined with good biocompatibility and minimal toxicity in vitro and in vivo support the potential of GQDs for future PDT application.

Imaging and Targeting of the α(2-6) and α(2-3) Linked Sialic Acid Quantum Dots in Zebrafish and Mouse Models.

Sialic acid-conjugated nanocarriers have emerged as attractive biomarkers with promising biomedical applications. The translation of these nanocarriers into clinical applications requires in-depth assessment in animal models. However, due to the complexity, ethical concerns, and cost of the high-order animal system, there is an immediate need of information-rich simple animal models to decipher the biological significance. Herein, we performed in vivo head-to-head comparison of Neu5Acα(2-6) and α(2-3)Gal conjugated quantum dots (QDs) toxicity, biodistribution, and sequestration in wild-type zebrafish ( Danio rerio) and mouse model (C57BL). The fluorescent properties and cadmium composition of quantum dots were used to map the blood clearance, biodistribution, and sequestration of the sialylated QDs in major organs of both models. We observed that α(2-6) sialylated QDs preferentially have prolonged circulating half-life and broader biodistribution in both models. On the contrary, α(2-3) sialic acid and galactose-conjugated QDs have shortened blood circulation time and are sequestered in the liver, and cleared after several hours in both models. These results demonstrate the applicability of the zebrafish and sialylated QDs to target specific organs, as well as drug delivery and biomedical diagnostics.

Antimicrobial and biocompatibility of highly fluorescent ZnSe core and ZnSe@ZnS core-shell quantum dots

Present study reports synthesis of Cd-free core-only and core-shell quantum dots (ZnSe of size 3.60 ± 0.12 nm and ZnSe@ZnS of size 4.80 ± 0.20 nm) having excellent fluorescent properties, stability, and aqueous solubility. The fluorescence behavior of these quantum dots (QDs) was utilized for cancer cell imaging and their comparative toxicity in cancerous (HeLa) and normal (HEK-293) cell lines was evaluated. The LC50 parameter of ZnSe (1.8 and 2.6 mg/ml) was significantly lower than that of ZnSe@ZnS (3.8 and 4.5 mg/ml) for the aforesaid cell lines which indicated higher toxicity of the core-only QD in comparison to the core-shell structure. Further, the cellular uptake and fluorescence intensity of core-shell QD was significantly higher. Furthermore, the antimicrobial property of both type of QDs was evaluated on microbes (Escherichia coli and Staphylococcus aureus) and core-shell structure was found to possess higher antimicrobial property towards gram-positive bacteria S. aureus, but was non-toxic to E. coli. These results suggested that surface modification of ZnSe with ZnS shell helps to enhance the fluorescence property and make these more biocompatible for biomedical applications. The non-toxicity towards E. coli also makes it suitable for labeling the microbial cell surface and for mapping the cellular metabolism.

Embryotoxicity of Quantum Dots in Rainbow Trout Oncorhynchus mykiss During the Hatching Period.

Due to the active development and application of nanotechnology, nanoparticles have emerged as a new class of environmental pollutants. The aim of the study was to investigate quantum dots (QDs) access routes and distribution in embryos and larvae of rainbow trout Oncorhynchus mykiss and to determine the toxicity of QDs to rainbow trout larvae depending on the duration of exposure. CdSe/ZnS-COOH QDs at sublethal concentration was used during the toxicity test (1, 4 and 14 days). The results showed that QDs could get from the solutions into the larvae after hatching. QDs induced a significant increase in mortality, gill ventilation frequency and behavioral responses and a decrease in relative body mass in larvae at the end of the test. Larvae exposed to QDs were found to possess developmental malformations (blood clots). It was found that biological responses of larvae significantly depended on the duration of exposure to QDs.

Synthesis, characterization and in vivo evaluation of cadmium telluride quantum dots toxicity in mice by toxicometabolomics approach

Quantum dots (QDs) have widespread application in many fields such as medicine and electronics. The need for understanding the potentially harmful side effects of these materials becomes clear. In this study, the toxicity of cadmium telluride quantum dots (CdTe-QDs) and bulk Cd2+ has been investigated and compared by applying metabolomics methods. The datasets were 1H-NMR data from mice plasma which had been taken from four groups of mice in different time intervals. Then, the data were analyzed by applying chemometrics methods and the metabolites were found from Human Metabolome Database (HMDB). The results showed the significant change in the level of some metabolites especially estrogenic steroids in different groups with different amounts of received Cd. The findings also indicated that steroid hormone biosynthesis, lysine biosynthesis and taurine and hypotaurine metabolism are the most affected pathways by CdTe-QDs especially in estrogenic steroids. The over-representation analysis indicated that endoplasmic reticulum, gonads, and hepatocytes are most affected. Since the pattern of metabolite alteration of CdTe-QDs with equivalent Cd2+ was similar to those of CdCl2, it was postulated that beside Cd2+ effects, the toxicity of CdTe-QDs is associated with other factors.