ABSTRACT
Despite the promising applications of the use of quantum dots (QDs) in the biomedical field, the long-lasting effects of QDs on the cell remain poorly understood. To comprehend the mechanisms underlying the toxic effects of QDs in yeast, we characterized defects associated with receptor-mediated endocytosis (RME) as well as pinocytosis using Saccharomyces cerevisiae as a model in the presence of cadmium selenide/zinc sulfide (CdSe/ZnS) QDs. Our findings revealed that QDs led to an inefficient RME at the early, intermediate, and late stages of endocytic patch maturation at the endocytic site, with the prolonged lifespan of GFP fused yeast fimbrin (Sac6-GFP), a late marker of endocytosis. The transit of FM1-43, a lipophilic dye from the plasma membrane to the vacuole, was severely retarded in the presence of QDs. Finally, QDs caused an accumulation of monomeric red fluorescent protein fused carbamoyl phosphate synthetase 1 (mRFP-Cps1), a vacuolar lumen marker in the vacuole. In summary, the present study provides novel insights into the possible impact of CdSe/ZnS QDs on the endocytic machinery, enabling a deeper comprehension of QD toxicity.
Subject(s)
Cadmium Compounds , Endocytosis , Quantum Dots , Saccharomyces cerevisiae , Selenium Compounds , Sulfides , Zinc Compounds , Quantum Dots/toxicity , Quantum Dots/chemistry , Endocytosis/drug effects , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/metabolism , Cadmium Compounds/toxicity , Selenium Compounds/toxicity , Sulfides/toxicity , Sulfides/metabolism , Zinc Compounds/toxicity , Vacuoles/metabolism , Vacuoles/drug effects , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae Proteins/genetics , Green Fluorescent Proteins/metabolism , Green Fluorescent Proteins/genetics , Cell Membrane/metabolism , Cell Membrane/drug effectsABSTRACT
Quantum dots (QDs) have been highly sought after in the past few decades for their potential to be used in many biomedical applications. However, QDs' cytotoxicity is still a major concern that limits the incorporation of QDs into cutting-edge technologies. Thus, it is important to study and understand the mechanism by which QDs exert their toxicity. Although many studies have explored the cytotoxicity of quantum dots through the transcriptomic level and reactive species generation, the impact of quantum dots on the expression of cellular protein remains unclear. Using Saccharomyces cerevisiae as a model organism, we studied the effect of cadmium selenide zinc sulfide quantum dots (CdSe/ZnS QDs) on the proteomic profile of budding yeast cells. We found a total of 280 differentially expressed proteins after 6 h of CdSe/ZnS QDs treatment. Among these, 187 proteins were upregulated, and 93 proteins were downregulated. The majority of upregulated proteins were found to be associated with transcription/RNA processing, intracellular trafficking, and ribosome biogenesis. On the other hand, many of the downregulated proteins are associated with cellular metabolic pathways and mitochondrial components. Through this study, the cytotoxicity of CdSe/ZnS QDs on the proteomic level was revealed, providing a more well-rounded knowledge of QDs' toxicity.
Subject(s)
Quantum Dots , Selenium Compounds , Saccharomyces cerevisiae , Proteomics , Zinc Compounds/toxicity , Sulfides/pharmacology , Selenium Compounds/toxicityABSTRACT
Commercially used quantum dots (QDs) exemplify complex nanomaterials with multiple components, though little is known about the type of interactions between these components in determining the overall toxicity of this material. We synthesized and characterized a functional QD (CdSe/ZnS_P&E) that was identical in structure and composition to a patented and commercially applied QD and the combinations of its components (CdSe, CdSe/ZnS, ZnS, CdSe_P&E, ZnS_P&E, and P&E). Cells exposed to incremental concentrations of these materials were investigated for cell viability and cellular perturbations, contributing to a final common pathway of cell death using high-content screening assays in model human intestinal epithelial cells (HIEC-6). The concentrations that resulted in a loss of 20% cell viability (EC20 values) for each tested component were used for estimating the combination index (CI) to evaluate synergistic or antagonistic effects between the components. Complete QD (core/shell-polymer) showed the highest toxic potential due to synergistic interactions between core and surface functional groups. The cationic polymer coating enhanced cellular uptake of the QD, ensuing lysosome acidification and release of heavy metal ions to the intracellular milieu, and caused oxidative stress and cytotoxicity. Overall, this study advances our understanding of the collective contribution of individual components of a functional QD toward its toxic potential and emphasizes the need to study multilayered nanomaterials in their entirety for hazard characterization.
Subject(s)
Cadmium Compounds , Metals, Heavy , Quantum Dots , Selenium Compounds , Cadmium Compounds/chemistry , Cadmium Compounds/toxicity , Humans , Metals, Heavy/toxicity , Polymers/chemistry , Quantum Dots/chemistry , Selenium Compounds/chemistry , Selenium Compounds/toxicity , Sulfides/chemistry , Zinc Compounds/chemistry , Zinc Compounds/toxicityABSTRACT
This paper presents a new method for the simultaneous speciation analysis of arsenic (As(III)-arsenite, As(V)-arsenate, DMA-dimethylarsinic acid, MMA-methylarsonic acid, and AsB-arsenobetaine) and selenium (Se(IV)-selenite, Se(VI)-selenate, Se-Methionine, and Se-Cystine), which was applied to a variety of seafood and onion samples. The determination of the forms of arsenic and selenium was undertaken using the High-Performance Liquid Chromatography Inductively Coupled Plasma Mass Spectrometry (HPLC-ICP-MS) analytical technique. The separation of both organic and inorganic forms of arsenic and selenium was performed using two analytical columns: an anion exchange column, Dionex IonPac AS22, containing an alkanol quaternary ammonium ion, and a double bed cation-anion exchange guard column, Dionex Ion Pac CG5A, containing, as a first layer, fully sulfonated latex for cation exchange and a fully aminated layer for anion exchange as the second layer. The ammonium nitrate, at pH = 9.0, was used as a mobile phase. The method presented here allowed us to separate the As and Se species within 10 min with a suitable resolution. The applicability was presented with different sample matrix types: seafood and onion.
Subject(s)
Arsenic/analysis , Food Contamination/analysis , Onions/chemistry , Onions/toxicity , Seafood/analysis , Seafood/toxicity , Selenium/analysis , Animals , Arsenic Poisoning , Arsenicals/analysis , Chromatography, High Pressure Liquid , Chromatography, Ion Exchange , Humans , Mass Spectrometry , Organoselenium Compounds/analysis , Organoselenium Compounds/toxicity , Selenium Compounds/analysis , Selenium Compounds/toxicityABSTRACT
Quantum dots (QDs) are new types of nanomaterials. Few studies have focused on the effect of different surface modified QDs on embryonic development. Herein, we compared the in vivo toxicity of CdSe/ZnS QDs with carboxyl (-COOH) and amino (-NH2) modification using zebrafish embryos. After exposure, the two CdSe/ZnS QDs decreased the survival rate, hatching rate, and embryo movement of zebrafish. Moreover, we found QDs attached to the embryo membrane before hatching and the eyes, yolk and heart after hatching. The attached amount of carboxyl QDs was more. Consistently, the Cd content in embryos and larvae was higher in carboxyl QD-treatment. We further observed that the two QDs caused zebrafish pericardial edema and cardiac dysfunction. In line with it, both carboxyl and amino QDs up-regulated the transcription levels of cardiac development-related genes, and the levels were higher in carboxyl QD-treated groups. Furthermore, the chelator of Cd2+ diethylene triamine pentacetate acid could partially rescued the developmental toxicity caused by the two types of QDs suggesting that both the nature of QDs and the release of Cd2+ contribute to the developmental toxicity. In conclusion, the two CdSe/ZnS QDs have developmental toxicity and affect the cardiac development, and the carboxyl QDs is more toxic possibly due to the higher affinity and more release to embryos and larvae. Our study provides new knowledge that the surface functional modification of QDs is critical on the development on aquatic species, which is beneficial to develop and applicate QDs more safely and environment-friendly.
Subject(s)
Cadmium Compounds , Quantum Dots , Selenium Compounds , Animals , Cadmium Compounds/toxicity , Quantum Dots/toxicity , Selenium Compounds/toxicity , Sulfides/toxicity , Zebrafish , Zinc Compounds/toxicityABSTRACT
Diseases caused by pathogenic bacilli pose an increasing threat to human health. A common feature of these bacteria is a complete cell wall; therefore, drugs that can penetrate this protective barrier could be used as a novel approach for treating these infections. Here we present a simple method for synthesizing a silica mesoporous material loaded with cadmium selenide (CdSe) and chlorogenic acid. Using UV-visible, fluorescence, and infrared imaging in combination with transmission electron microscopy, it was shown that CdSe and chlorogenic acid could be successfully embedded in the mesopores of silica nanoparticles (CSC NPs), and these NPs presented with a strong fluorescence, uniform size, and good dispersion. Additionally, the results of these analyses indicated that the fluorescence of the CSC NPs was localized within the cells of Escherichia coli and Bacillus subtilis, signifying that these NPs could breach the cell wall and enter the cells of these two bacilli. Additional assessments found that these CSC NPs inhibited the proliferation of the bacteria by disrupting the cell wall, and this was most likely due to the overproduction of reactive oxygen species induced by chlorogenic acid. Importantly, histopathology analysis indicated that the CSC NPs had limited side effects and high biocompatibility.
Subject(s)
Anti-Bacterial Agents/pharmacology , Chlorogenic Acid/pharmacology , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Silicon Dioxide/pharmacology , Animals , Bacillus subtilis/drug effects , Bacillus subtilis/ultrastructure , Cadmium Compounds/toxicity , Chlorogenic Acid/toxicity , Escherichia coli/drug effects , Escherichia coli/ultrastructure , Male , Mice, Nude , Microbial Sensitivity Tests , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Porosity , Reference Standards , Selenium Compounds/toxicityABSTRACT
The interactions between adenosine triphosphate-binding cassette (ABC) transporters and nano-sized materials are attracting increasing attention, due to their great potential in overcoming the multidrug resistance (MDR) phenomena in cancer treatment. However, the inner mechanisms involved in the interactions are largely unknown. In this study, two commercial quantum dots (QDs), CdSe/ZnS-MPA and CdSe/ZnS-GSH, were tested for their interactions with P-glycoprotein (P-gp), as well as the relating mechanisms in lung cancer (A549) cells. Both QDs significantly suppressed the gene and protein expressions of P-gp in A549 cells. To explain this, the gene expressions of nine relating microRNAs (miRNAs) were evaluated. The results indicated a shared up-regulation of miR-34b and miR-185 by both QDs. Furthermore, mimics and inhibitors of miR-34b and miR-185 significantly enhanced and suppressed the gene and protein expressions of P-gp, respectively, confirming the modulatory function of these two miRNAs on P-gp. Interestingly, expressions of both miRNAs were suppressed during treatment with Cd2+ and doxorubicin, which induced the expression of P-gp, indicating the universality of these miRNAs-related mechanisms. Thus, as miR-34b and miR-185 participated in the suppression of P-gp functions in A549 cells they could be interesting targets for the treatment of lung cancer.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Cadmium Compounds/toxicity , Gene Expression Regulation, Neoplastic/drug effects , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Quantum Dots/toxicity , Selenium Compounds/toxicity , Sulfides/toxicity , Zinc Compounds/toxicity , A549 Cells , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Cadmium Chloride/toxicity , Down-Regulation , Doxorubicin/toxicity , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/genetics , Risk AssessmentABSTRACT
In recent years quantum dots (QDs) have risen as useful luminescent nanoparticles with multiple applications ranging from laser, image displays and biomedical applications. Here we review and discuss the studies of these nanoparticles in patient derived cellular samples or tissues, including cellular models from iPSCs from patients, biopsied and post-mortem tissue. QD-based multiplexed imaging has been proved to overcome most of the major drawbacks of conventional techniques, exhibiting higher sensitivity, reliability, accuracy and simultaneous labeling of key biomarkers. In this sense, QDs are very promising tools to be further used in clinical applications including diagnosis and therapy approaches. Analyzing the possibilities of these materials in these biological samples gives an overview of the future applications of the nanoparticles in models closer to patients and their specific disease.
Subject(s)
Cadmium Compounds/chemistry , Models, Biological , Quantum Dots/chemistry , Selenium Compounds/chemistry , Cadmium Compounds/toxicity , Female , Humans , Male , Neoplasms/pathology , Quantum Dots/toxicity , Reproducibility of Results , Selenium Compounds/toxicityABSTRACT
Quantum dots (QDs), such as cadmium selenide (CdSe) and lead selenide (PbSe) exhibit excellent optical, magnetic and chemical properties due to their extremely size (ca. 1-10 nm) and are attractive semiconductor nanomaterials for optical studies and energy storage. In this study, aqueous synthesis of CdSe and PbSe QDs in a size range of 2-10 nm was described. Synthesized QDs were characterized using SEM and TEM, DLS, zeta potential, FTIR, EDX and XRD. Highest accumulation (72.5 ± 5.8 mg L-1) of PbSe QDs occurred at 10 ppm suspensions. In general accumulation increased up to 48 h exposure then fluctuate tended to decline. For CdSe QDs, accumulation tended to decrease for 72 h exposure except that for 5 ppm groups. For the elimination period, in general, the elimination levels of PbSe and CdSe QDs from exposed individuals decreased (p < 0.05) even it has some fluctuate.
Subject(s)
Artemia/physiology , Cadmium Compounds/toxicity , Lead/toxicity , Quantum Dots/toxicity , Selenium Compounds/toxicity , Animals , Artemia/drug effects , Cadmium Compounds/chemistry , Cadmium Compounds/pharmacology , Nanostructures , Water/chemistryABSTRACT
We studied changes in the transcription of genes encoding cytokines (TNF, IL-6, IL-10, and IL-32), cell activation markers (ICAM1, CD38, Fas, and FCGRIII), ROS production catalyst (NOX2), autophagy (Beclin 1, LC3B, and p62) and apoptosis (BAX, BCL2) regulators in peripheral blood mononuclear cells upon contact with quantum dots CdSe/ZnS-MPA and CdSe/CdSeZnS/ZnS-PTVP. Up-regulation of TNF, ICAM1, Fas, p62 mRNA and down-regulation of the FCGRIII and NOX2 mRNA in response to the presence of quantum dots were revealed. The formation of serum protein corona on the surface of quantum dots abolished this effect.
Subject(s)
Inflammation/genetics , Leukocytes, Mononuclear/drug effects , Protein Corona/chemistry , Quantum Dots , Adult , Apoptosis/drug effects , Autophagy/drug effects , Cadmium Compounds/pharmacology , Cadmium Compounds/toxicity , Cytokines/metabolism , Gene Expression/drug effects , Humans , Inflammation Mediators/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Quantum Dots/chemistry , Quantum Dots/toxicity , Reactive Oxygen Species/metabolism , Selenium Compounds/pharmacology , Selenium Compounds/toxicity , Zinc Compounds/pharmacology , Zinc Compounds/toxicityABSTRACT
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.
Subject(s)
Cadmium Compounds/toxicity , Chlorella/drug effects , Environmental Pollutants/toxicity , Quantum Dots/toxicity , Scenedesmus/drug effects , Selenium Compounds/toxicity , Chlorella/growth & development , Chlorella/metabolism , Chlorophyll/metabolism , Dose-Response Relationship, Drug , Malondialdehyde/metabolism , Metallurgy , Scenedesmus/growth & development , Scenedesmus/metabolism , Superoxide Dismutase/metabolismABSTRACT
The present study focused on the bioaccumulation and cytotoxicities of Cd2+, CdSe quantum dots (QDs) and CdSe/ZnS QDs in Escherichia coli (E. coli, represents prokaryotic system) and Phanerochaete chrysosporium (P. chrysosporium, represents eukaryotic system), respectively. Two types of QDs were characterized by transmission electron microscopy (TEM) and dynamic light scattering. The inductively coupled plasma optical emission spectrometer results showed that the bioaccumulation amounts of CdSe QDs by E. coli and P. chrysosporium were larger than those of CdSe/ZnS QDs due to the smaller particle size and less negative surface charges of CdSe QDs. Confocal microscopy and TEM results showed that there was an interaction between QDs and cells, and QDs have entered into the cells eventually, leading to the change of cell morphology. Plasma membrane fluidities and membrane H+-ATPase activities of E. coli and P. chrysosporium decreased gradually with the increasing concentrations of Cd2+, CdSe and CdSe/ZnS QDs. Results of the cell viabilities and intracellular reactive oxygen species levels indicated that the induced cytotoxicities were decreased as follows: CdSe QDsâ¯>â¯CdSe/ZnS QDsâ¯>â¯Cd2+. These findings suggested that the cytotoxicity of QDs was not only attributed to their heavy metal components, but also related to their nanosize effects which could induce particle-specific toxicity. The above results offer valuable information for exploring the cytotoxicity mechanism of QDs in prokaryote and eukaryote.
Subject(s)
Cadmium Compounds/toxicity , Cadmium/toxicity , Quantum Dots/toxicity , Selenium Compounds/toxicity , Sulfides/toxicity , Zinc Compounds/toxicity , Cytotoxins/metabolism , Cytotoxins/toxicity , Escherichia coli/drug effects , Escherichia coli/metabolism , Escherichia coli/ultrastructure , Ions , Membrane Fluidity/drug effects , Microbial Viability/drug effects , Phanerochaete/drug effects , Phanerochaete/ultrastructure , Quantum Dots/metabolism , Reactive Oxygen Species/metabolism , Sulfides/metabolism , Zinc Compounds/metabolismABSTRACT
Four types of quantum dots (QDs) with varying emission wavelengths were synthesized in this study. The dots included CdSe and CdSe/ZnS core/shell QDs with short emission wavelengths of 540 nm and 560 nm, respectively, as well as CdSe and CdSe/ZnS core/shell QDs with longer emission wavelengths of 585 nm and 595 nm, respectively. The ligands on the QD surfaces were exchanged with mercaptopropionic acid (MPA) to make them water-soluble. The efficiency of singlet oxygen (1O2) production from both CdSe and CdSe/ZnS core/shell QDs was highest at a QD concentration of 14 µg/ml Singlet oxygen production from the CdSe QDs was higher than that with the CdSe/ZnS core/shell QDs after 1 h of LED470 irradiation. However, the singlet oxygen production of CdSe/ZnS core/shell QDs was much higher than that of CdSe QDs at concentrations above 14 µg/ml. The cytotoxicities of both CdSe and CdSe/ZnS core/shell QDs were investigated using HeLa cells.
Subject(s)
Cadmium Compounds/toxicity , Quantum Dots , Selenium Compounds/toxicity , HeLa Cells , Humans , Singlet Oxygen , Sulfides , Zinc CompoundsABSTRACT
INTRODUCTION: Concerns have been raised regarding occupational exposure to engineered nanomaterials (ENMs). Potential impacts on lung function from inhalation exposures are of concern as the lung is a sensitive ENM target in animals. Epidemiological data suggest that occupational exposure to ENMs may impact respiratory and cardiovascular health. Quantum dots (QDs) are ENMs with outstanding semiconductor and fluorescent properties with uses in biomedicine and electronics. QDs are known to induce inflammation and cytotoxicity in rodents and high dose exposures impact lung function 2 weeks after exposure. However, effects of mouse strain and the temporality of QD effects on lung function at more occupationally relevant doses have not been well-established. OBJECTIVE: We evaluated the impact of QD exposure on respiratory mechanics in C57BL/6J and A/J mice. Previous work found a greater initial inflammatory response to QD exposure in A/J mice compared to C57BL/6J mice. Thus, we hypothesized that A/J mice would be more sensitive to QD-induced effects on lung mechanics. METHODS: C57BL/6J and A/J mice were exposed to 6 µg/kg Cd equivalents of amphiphilic polymer-coated Cd/Se core, ZnS shell QDs via oropharyngeal aspiration. Lung mechanics were measured using forced oscillation, and inflammation was characterized by neutrophils and cytokines in bronchoalveolar lavage fluid. RESULTS: Both strains showed signs of QD-induced acute lung inflammation. However, lung mechanics were impacted by QD exposure in A/J mice only. CONCLUSIONS: Our findings suggest that susceptibility to QDs and similar ENM-induced changes in lung function may depend at least in part on genetic background.
Subject(s)
Inhalation Exposure/adverse effects , Lung/drug effects , Quantum Dots/toxicity , Respiratory Mechanics , Animals , Bronchoalveolar Lavage Fluid , Cadmium Compounds/toxicity , Cytokines , Inflammation , Lung/physiopathology , Mice , Mice, Inbred A , Mice, Inbred C57BL , Neutrophils , Selenium Compounds/toxicity , Time FactorsABSTRACT
In the marine environment, benthic diatoms from estuarine and coastal sediments are among the first targets of nanoparticle pollution whose potential toxicity on marine organisms is still largely unknown. It is therefore relevant to improve our knowledge of interactions between these new pollutants and microalgae, the key players in the control of marine resources. In this study, the response of P. tricornutum to CdSe nanocrystals (CdSe NPs) of 5â¯nm (NP5) and 12â¯nm (NP12) in diameter was evaluated through microscopic, physiological, biochemical and proteomic approaches. NP5 and NP12 affected cell growth but oxygen production was only slightly decreased by NP5 after 1-d incubation time. In our experimental conditions, a high CdSe NP dissolution was observed during the first day of culture, leading to Cd bioaccumulation and oxidative stress, particularly with NP12. However, after a 7-day incubation time, proteomic analysis highlighted that P. tricornutum responded to CdSe NP toxicity by regulating numerous proteins involved in protection against oxidative stress, cellular redox homeostasis, Ca2+ regulation and signalling, S-nitrosylation and S-glutathionylation processes and cell damage repair. These proteome changes allowed algae cells to regulate their intracellular ROS level in contaminated cultures. P. tricornutum was also capable to control its intracellular Cd concentration at a sufficiently low level to preserve its growth. To our knowledge, this is the first work allowing the identification of proteins differentially expressed by P. tricornutum subjected to NPs and thus the understanding of some molecular pathways involved in its cellular response to nanoparticles. SIGNIFICANCE: The microalgae play a key role in the control of marine resources. Moreover, they produce 50% of the atmospheric oxygen. 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. Since estuarine and coastal sediments concentrate pollutants, benthic microalgae which live in superficial sediments will be among the first targets of nanoparticle pollution. Thus, it is relevant to improve our knowledge of interactions between diatoms and nanoparticles. Proteomics is a powerful tool for understanding the molecular mechanisms triggered by nanoparticle exposure, and our study is the first one to use this tool to identify proteins differentially expressed by P. tricornutum subjected to CdSe nanocrystals. This work is fundamental to improve our knowledge about the defence mechanisms developed by algae cells to counteract damage caused by CdSe NPs.
Subject(s)
Cadmium Compounds/toxicity , Diatoms/drug effects , Nanoparticles/toxicity , Oxidative Stress/drug effects , Proteome/metabolism , Selenium Compounds/toxicity , Water Pollutants, Chemical/toxicity , Calcium Signaling/drug effects , Diatoms/metabolism , Mass Spectrometry , Microalgae/drug effects , Microalgae/metabolism , ProteomicsABSTRACT
A clear consequence of the increasing application of nanotechnology is its adverse effect on the environment. Semiconductor nanoparticles are among engineered nanomaterials that have been considered recently for their specific characteristics. In the present work, zinc selenide nanoparticles (ZnSe NPs) were synthesized and characterized by XRD, TEM, DLS and SEM. Biological aspects related to the impact of nanoparticles and Zn2+ ions were analyzed on the aquatic higher plant Lemna minor. The localization of ZnSe NPs in the root cells of L. minor was determined by TEM and fluorescence microscopy. Then, the entrance of ZnSe NPs into the plant cells was evaluated by a range of biological tests. The outcomes revealed that both the NPs and the ionic forms noticeably poisoned L. minor. In one hand, growth parameters and physiological indices such as photosynthetic pigments content were decreased. On the other hand, the activities of some antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), as well as the contents of nonenzymatic antioxidants (phenols and flavonoids) were elevated. Taken together, high concentration of ZnSe NPs and Zn2+ triggered phytotoxicity which in turn provoked the plants' defense system. The changes in antioxidant activities confirmed a higher toxicity by Zn2+ ions in comparison with ZnSe NPs. It means that the considered ions are more hazardous to the living organisms than the nanoparticles.
Subject(s)
Metal Nanoparticles/toxicity , Selenium Compounds/toxicity , Zinc Compounds/toxicity , Antioxidants , Araceae , Catalase , Superoxide Dismutase , Zinc OxideABSTRACT
Theranostic nanoprobes integrated with diagnostic imaging and therapy capabilities have shown great potential for highly effective tumor therapy by realizing imaging-guided drug delivery and tumor treatment. Developing novel high-performance nanoprobes is an important basis for tumor theranostic application. Here, near-infrared (NIR) fluorescent and low-biotoxicity Ag2 Se quantum dots (QDs) have been coupled with cetuximab, a clinical antiepidermal growth factor receptor antibody drug for tumor therapy, via a facile bioconjugation strategy to prepare multifunctional Ag2 Se-cetuximab nanoprobes. Compared with the Ag2 Se QDs alone, the Ag2 Se-cetuximab nanoprobes display faster and more enrichment at the site of orthotopic tongue cancer, and thus present better NIR fluorescence contrast between the tumor and the surrounding regions. At 24 h postinjection, the NIR fluorescence of Ag2 Se-cetuximab nanoprobes at the tumor site is still easily detectable, whereas no fluorescence is observed for the Ag2 Se QDs. Moreover, the Ag2 Se-cetuximab nanoprobes have also significantly inhibited the tumor growth and improved the survival rate of orthotopic tongue cancer-bearing nude mice from 0% to 57.1%. Taken together, the constructed multifunctional Ag2 Se-cetuximab nanoprobes have achieved combined targeted imaging and therapy of orthotopic tongue cancer, which may greatly contribute to the development of nanotheranostics.
Subject(s)
Cetuximab/therapeutic use , Diagnostic Imaging , Infrared Rays , Nanoparticles/chemistry , Selenium Compounds/chemistry , Silver/chemistry , Tongue Neoplasms/diagnosis , Tongue Neoplasms/drug therapy , Animals , Cell Death/drug effects , Cell Line , Female , Fluorescence , Humans , Hydrophobic and Hydrophilic Interactions , Mice, Inbred BALB C , Quantum Dots/ultrastructure , Selenium Compounds/toxicity , Silver/toxicity , Solubility , Surface Properties , Survival Analysis , Theranostic Nanomedicine , Time Factors , Tongue Neoplasms/pathology , Treatment Outcome , Water/chemistryABSTRACT
BACKGROUND: Nanoparticle interactions with cellular membranes and the kinetics of their transport and localization are important determinants of their functionality and their biological consequences. Understanding these phenomena is fundamental for the translation of such NPs from in vitro to in vivo systems for bioimaging and medical applications. Two CdSe/ZnS quantum dots (QD) with differing surface functionality (NH2 or COOH moieties) were used here for investigating the intracellular uptake and transport kinetics of these QDs. RESULTS: In water, the COOH- and NH2-QDs were negatively and positively charged, respectively, while in serum-containing medium the NH2-QDs were agglomerated, whereas the COOH-QDs remained dispersed. Though intracellular levels of NH2- and COOH-QDs were very similar after 24 h exposure, COOH-QDs appeared to be continuously internalised and transported by endosomes and lysosomes, while NH2-QDs mainly remained in the lysosomes. The results of (intra)cellular QD trafficking were correlated to their toxicity profiles investigating levels of reactive oxygen species (ROS), mitochondrial ROS, autophagy, changes to cellular morphology and alterations in genes involved in cellular stress, toxicity and cytoskeletal integrity. The continuous flux of COOH-QDs perhaps explains their higher toxicity compared to the NH2-QDs, mainly resulting in mitochondrial ROS and cytoskeletal remodelling which are phenomena that occur early during cellular exposure. CONCLUSIONS: Together, these data reveal that although cellular QD levels were similar after 24 h, differences in the nature and extent of their cellular trafficking resulted in differences in consequent gene alterations and toxicological effects.
Subject(s)
Autophagy/drug effects , Cadmium Compounds/toxicity , Quantum Dots/toxicity , Reactive Oxygen Species/metabolism , Selenium Compounds/toxicity , Sulfides/toxicity , Zinc Compounds/toxicity , Cadmium Compounds/analysis , Cadmium Compounds/metabolism , Cell Line , Gene Expression Regulation/drug effects , Humans , Lysosomes/drug effects , Lysosomes/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Quantum Dots/analysis , Quantum Dots/metabolism , Selenium Compounds/analysis , Selenium Compounds/metabolism , Sulfides/analysis , Sulfides/metabolism , Zinc Compounds/analysis , Zinc Compounds/metabolismABSTRACT
BACKGROUND: When evaluating the toxicity of engineered nanomaterials (ENMS) it is important to use multiple bioassays based on different mechanisms of action. In this regard we evaluated the use of gene expression and common cytotoxicity measurements using as test materials, two selected nanoparticles with known differences in toxicity, 5 nm mercaptoundecanoic acid (MUA)-capped InP and CdSe quantum dots (QDs). We tested the effects of these QDs at concentrations ranging from 0.5 to 160 µg/mL on cultured normal human bronchial epithelial (NHBE) cells using four common cytotoxicity assays: the dichlorofluorescein assay for reactive oxygen species (ROS), the lactate dehydrogenase assay for membrane viability (LDH), the mitochondrial dehydrogenase assay for mitochondrial function, and the Comet assay for DNA strand breaks. RESULTS: The cytotoxicity assays showed similar trends when exposed to nanoparticles for 24 h at 80 µg/mL with a threefold increase in ROS with exposure to CdSe QDs compared to an insignificant change in ROS levels after exposure to InP QDs, a twofold increase in the LDH necrosis assay in NHBE cells with exposure to CdSe QDs compared to a 50% decrease for InP QDs, a 60% decrease in the mitochondrial function assay upon exposure to CdSe QDs compared to a minimal increase in the case of InP and significant DNA strand breaks after exposure to CdSe QDs compared to no significant DNA strand breaks with InP. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) data for cells exposed for 6 h at a concentration of 80 µg/mL were consistent with the cytotoxicity assays showing major differences in DNA damage, DNA repair and mitochondrial function gene regulatory responses to the CdSe and InP QDs. The BRCA2, CYP1A1, CYP1B1, CDK1, SFN and VEGFA genes were observed to be upregulated specifically from increased CdSe exposure and suggests their possible utility as biomarkers for toxicity. CONCLUSIONS: This study can serve as a model for comparing traditional cytotoxicity assays and gene expression measurements and to determine candidate biomarkers for assessing the biocompatibility of ENMs.
Subject(s)
Biological Assay , Cadmium Compounds/toxicity , Epithelial Cells/drug effects , Fatty Acids/toxicity , Nanoparticles/toxicity , Quantum Dots/toxicity , Selenium Compounds/toxicity , Sulfhydryl Compounds/toxicity , BRCA2 Protein/genetics , BRCA2 Protein/metabolism , Biomarkers/metabolism , Bronchi/cytology , Bronchi/drug effects , Bronchi/metabolism , Cell Line , Cell Membrane/chemistry , Cell Membrane/drug effects , Cell Membrane/metabolism , Comet Assay , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Epithelial Cells/cytology , Epithelial Cells/metabolism , Fluoresceins/chemistry , Fluorescent Dyes/chemistry , Gene Expression/drug effects , Humans , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Nucleic Acid Denaturation/drug effects , Oxidoreductases/genetics , Oxidoreductases/metabolism , Reactive Oxygen Species/agonists , Reactive Oxygen Species/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Toxicity of selenomethionine, an organic derivative of selenium widely used as supplement in human diets, was studied in the model organism Saccharomyces cerevisiae. Several DNA repair-deficient strains hypersensitive to selenide displayed wild-type growth rate properties in the presence of selenomethionine indicating that selenide and selenomethionine exert their toxicity via distinct mechanisms. Cytotoxicity of selenomethionine decreased when the extracellular concentration of methionine or S-adenosylmethionine was increased. This protection resulted from competition between the S- and Se-compounds along the downstream metabolic pathways inside the cell. By comparing the sensitivity to selenomethionine of mutants impaired in the sulfur amino acid pathway, we excluded a toxic effect of Se-adenosylmethionine, Se-adenosylhomocysteine, or of any compound in the methionine salvage pathway. Instead, we found that selenomethionine toxicity is mediated by the trans-sulfuration pathway amino acids selenohomocysteine and/or selenocysteine. Involvement of superoxide radicals in selenomethionine toxicity in vivo is suggested by the hypersensitivity of a Δsod1 mutant strain, increased resistance afforded by the superoxide scavenger manganese, and inactivation of aconitase. In parallel, we showed that, in vitro, the complete oxidation of the selenol function of selenocysteine or selenohomocysteine by dioxygen is achieved within a few minutes at neutral pH and produces superoxide radicals. These results establish a link between superoxide production and trans-sulfuration pathway seleno-amino acids and emphasize the importance of the selenol function in the mechanism of organic selenium toxicity.