Cytotoxicity Of Quantum Dots Research Articles

Studies of Intracorneal Distribution and Cytotoxicity of Quantum Dots: Risk Assessment of Eye Exposure

The cornea is a potential route of exposure and drug administration for nanoparticles. In this work, we use noninvasive two-photon microscopic imaging to study the distribution and permeability pathway of CdSe/ZnS core/shell quantum dots (QDs) capped with three different functional groups through the cornea. With no additional staining, the two-photon image clearly discloses that fluorescent QDs penetrate and reside within the interlamellar space of second harmonic generating collagenous stroma when the corneal epithelium barrier is injured. An in vitro cytotoxicity test using bovine corneal stromal cells incubated individually with all three kinds of QDs indicates that the cell viability decreases significantly as the QD concentration and incubation period increased. The results also show that the specific QDs influence corneal stromal cell viability up to a significant magnitude of 50% under a relatively low concentration (5-20 nM) and short exposure period (24-48 h). Furthermore, two-photon imaging shows that QDs can be retained within the cornea up to 26 days in an in vivo mouse model. On the basis of our in vivo and in vitro data, we conclude that QDs can penetrate and be retained within cornea long enough to cause consequential cytotoxicity, under the circumstance in which the corneal epithelium barrier is injured. Since corneal abrasion is quite a common situation in daily life, our work raises public attention to the potential risk of eye exposure to nanoparticles.

Quantum dots affect expression of CD133 surface antigen in melanoma cells.

BackgroundIn novel treatment approaches, therapeutics should be designed to target cancer stem cells (CSCs). Quantum dots (QDs) are a promising new tool in fighting against cancer. However, little is known about accumulation and cytotoxicity of QDs in CSCs.MethodsAccumulation and cytotoxicity of CdTe-MPA (mercaptopropionic acid) QDs in CSCs were assessed using flow cytometry and fluorescence-activated cell sorting techniques as well as a colorimetric cell viability assay.ResultsWe investigated the expression of two cell surface-associated glycoproteins, CD44 and CD133, in four different cancer cell lines (glioblastoma, melanoma, pancreatic, and prostate adenocarcinoma). Only the melanoma cells were positive to both markers of CD44 and CD133, whereas the other cells were only CD44-positive. The QDs accumulated to a similar extent in all subpopulations of the melanoma cells. The phenotypical response after QD treatment was compared with the response after ionizing radiation treatment. The percentage of the CD44high−CD133high subpopulation decreased from 72% to 55%–58% for both treatments. The stem-like subpopulation CD44highCD133low/− increased from 26%–28% in the untreated melanoma cells to 36%–40% for both treatments.ConclusionTreatment of melanoma cells with QDs results in an increase of stem-like cell subpopulations. The changes in phenotype distribution of the melanoma cells after the treatment with QDs are comparable with the changes after ionizing radiation.

Bioeffects of CdTe Quantum Dots on Human Umbilical Vein Endothelial Cells

Quantum dots (QDs) hold great potential for applications in nanomedicine, however, their health effects are largely unknown. In the present study, the cytotoxicity and genotoxicity of CdTe QDs were examined in human umbilical vein endothelial cells (HUVECs). The QDs exhibited a dose-dependent inhibitory effect on cell growth. It was shown that after a 12 h treatment QDs at 1, 10, and 50 microg x ml(-1) induced formation of yH2AX foci, indicative of DNA damage, in a dose-dependent manner. Moreover, QD treatment clearly induced the generation of reactive oxygen species (ROS). Pre-treatment with N-acetyl-cysteine (NAC), a ROS scavenger, could inhibit the induction of ROS by QDs, as well as the formation of yH2AX foci. Taken together, our data indicate that CdTe QDs have cytotoxic and genotoxic effects on HUVECs, and that ROS generation may be involved in QD induced DNA damage.

THE ROLES OF PHOTOLUMINESCENT QUANTUM DOTS IN GENERATION OR DETECTION OF REACTIVE OXYGEN SPECIES: CULPRITS OR DETECTIVES?

In this review, we systematically analyzed the complicated interrelationship between photoluminescent quantum dots (QDs) and reactive oxygen species of biological importance. QDs, when photoexcited, generate reactive oxygen species (ROS), which are partially blamed for the cytotoxicity of QDs. On the positive side, the ability of generating ROS by QDs are exploited in photodynamic therapy using QDs alone or in combination with QD-surface bound organic sensitizers via resonance energy transfer from QDs to the organic dyes. Lastly, depending on the chemical composition and the functionalization of the QDs, ROS are known to quench or switch-on the QD photoluminescence. The selectivity and sensitivity toward specific ROS can be achieved through judicious chemical modification of QD surface coating layers by taking into account the reactivity difference among different ROS. The flexible QD surface functionalization opens up the unprecedented possibility of designer-made nanoprobes for sensing and quantifying ROS of biological importance.

Quantum dot cytotoxicity in vitro: An investigation into the cytotoxic effects of a series of different surface chemistries and their core/shell materials

The aim of this study was to assess the effects of a series of different surface coated quantum dots (QDs) (organic, carboxylated [COOH] and amino [NH2] polytethylene glycol [PEG]) on J774.A1 macrophage cell viability and to further determine which part of the QDs cause such toxicity. Cytotoxic examination (MTT assay and LDH release) showed organic QDs to induce significant cytotoxicity up to 48 h, even at a low particle concentration (20 nM), whilst both COOH and NH2 (PEG) QDs caused reduced cell viability and cell membrane permeability after 24 and 48 h exposure at 80 nM. Subsequent analysis of the elements that constitute the QD core, core/shell and (organic QD) surface coating showed that the surface coating drives QD toxicity. Elemental analysis (ICP-AES) after 48 h, however, also observed a release of Cd from organic QDs. In conclusion, both the specific surface coating and core material can have a significant impact on QD toxicity.

Assessment of cytocompatibility of surface-modified CdSe/ZnSe quantum dots for BALB/3T3 fibroblast cells

With the widespread use of quantum dots (QDs), the likelihood of exposure to QDs has been assumed to have increased substantially. Recently, QDs have been employed in numerous biological and medical applications. However, there is a lack of toxicological data pertaining to QDs. In this study, we aimed to investigate the cytocompatibility of surface-modified CdSe/ZnSe QDs for BALB/3T3 fibroblast cells. The ligands used for surface modification are mercaptopropionic acid (MPA) and Gum arabic (GA)/tri-n-octylphosphine oxide (TOPO). Cells were exposed to different concentrations of QDs followed by illustrative cytotoxicity analyses. Furthermore, we used a confocal microscope to assess intracellular uptake of QDs. Confocal images showed that MPA-coated QDs were distributed inside the cytoplasmic region of cells. In contrast, GA/TOPO-coated QDs were not found inside cells. MPA-coated QDs were highly cytocompatible, whereas GA/TOPO-coated QDs were toxic to the cells. Cells treated with GA/TOPO-coated QDs showed altered morphology, decreased viability, significant concentrations of intracellular free cadmium, detectable reactive oxygen species (ROS) formation, depolymerized cytoskeleton, and irregular-shaped nuclei. This study suggests that surface modification by ligands plays a significant role in the prevention of cytotoxicity of QDs.

The cytotoxicity of CdTe quantum dots and the relative contributions from released cadmium ions and nanoparticle properties

A systematic study was carried out on the relationship between the cytotoxicity of quantum dots (QDs) and free cadmium ions using CdCl2 solution with known amounts of Cd2+ as the control. We found that the CdTe QDs were more cytotoxic than CdCl2 solutions even when the intracellular Cd2+ concentrations were identical in HEK293 cells treated with them, implying the cytotoxicity of CdTe QDs cannot attributed solely to the toxic effect of free Cd2+. Moreover, we discovered that the cytotoxicity of QDs was based on the concentration of total QDs ingested by cells. Our data clearly showed that specific properties of nanopartices have an obvious influence on their cytotoxicity.

Spatial control of cells, peptide delivery and dynamic monitoring of cellular physiology with chitosan-assisted dual color quantum dot FRET peptides

Cell-based assays have become important tools in the pharmaceutical and biotechnology industries. However, observing and monitoring molecules in cells that mimic the physiological environment is often difficult. Dynamic processes not only increase the accuracy of simulations, but also improve our understanding of the function and regulation of molecules within cells. In this study we used chitosan as a multifunctional biomaterial for selective micropatterning of cells, peptide delivery and covalent bonding with quantum dots (QD) to decrease the cytotoxicity of QD. Our results demonstrate the efficacy of chitosan-QD-peptide-Alexa Fluor 488 in controlling the spread and spatial organization of cells. Cationic chitosan also provided an efficient delivery mechanism to live cells. We used the shift from green to red fluorescence of the chitosan dual color QD peptide to detect biological activity. This methodology has potential applications in high throughput screening of inhibitors and activators of biological mechanisms and pathways and for use in the pharmaceutical industry.

In vitro and in vivo imaging with quantum dots

Quantum dots (QDs), also named semiconductor nanocrystals, have initiated a new realm of bioscience by combining nanomaterials with biology, which will profoundly influence future biological and biomedical research. In this review, we describe the extraordinary optical properties of QDs and developments in methods for their synthesis. We focus on fluorescent imaging with QDs both in vitro and in vivo, and the cytotoxicity of QDs and potential barriers to their use in practical biomedical applications. Finally, we provide insights into improvements aimed at decreasing the cytotoxicity of QDs and the future outlook of QD applications in biomedical fields.

The impact of CdSe/ZnS Quantum Dots in cells of Medicago sativa in suspension culture

BackgroundNanotechnology has the potential to provide agriculture with new tools that may be used in the rapid detection and molecular treatment of diseases and enhancement of plant ability to absorb nutrients, among others. Data on nanoparticle toxicity in plants is largely heterogeneous with a diversity of physicochemical parameters reported, which difficult generalizations. Here a cell biology approach was used to evaluate the impact of Quantum Dots (QDs) nanocrystals on plant cells, including their effect on cell growth, cell viability, oxidative stress and ROS accumulation, besides their cytomobility.ResultsA plant cell suspension culture of Medicago sativa was settled for the assessment of the impact of the addition of mercaptopropanoic acid coated CdSe/ZnS QDs. Cell growth was significantly reduced when 100 mM of mercaptopropanoic acid -QDs was added during the exponential growth phase, with less than 50% of the cells viable 72 hours after mercaptopropanoic acid -QDs addition. They were up taken by Medicago sativa cells and accumulated in the cytoplasm and nucleus as revealed by optical thin confocal imaging. As part of the cellular response to internalization, Medicago sativa cells were found to increase the production of Reactive Oxygen Species (ROS) in a dose and time dependent manner. Using the fluorescent dye H2DCFDA it was observable that mercaptopropanoic acid-QDs concentrations between 5-180 nM led to a progressive and linear increase of ROS accumulation.ConclusionsOur results showed that the extent of mercaptopropanoic acid coated CdSe/ZnS QDs cytotoxicity in plant cells is dependent upon a number of factors including QDs properties, dose and the environmental conditions of administration and that, for Medicago sativa cells, a safe range of 1-5 nM should not be exceeded for biological applications.

Untargeted quantum dots in confocal microscopy of living cells

The problem of non-specific binding of quantum dots (QDs) with cells is very important but not fully understood taking into account the possible application of QDs in medical and fundamental studies. The interactions of untargeted CdSe/ZnS QDs with isolated frog muscle fibres, HeLa cells and J774 cells were investigated. The observations were performed on living cells using laser confocal microscopy (Leica TCS SL). The QDs covered with polyethylenglycol without any functional reactive groups with emission maximum at 565 nm were used in the study. This type of QDs is suggested to prevent an interaction of QDs with biological molecules. It has been shown that QDs do not enter HeLa cells, T-system and sarcoplasm of skeletal muscle fibres. However, during long-term incubation J774 cells can uptake QDs. The data obtained has demonstrated the diversity of interactions of untargeted QDs with different cell types and are important for understanding of the problems of non-selective uptake and cytotoxicity of QDs.

The effect of quantum dots on synaptic transmission and plasticity in the hippocampal dentate gyrus area of anesthetized rats

Recently, quantum dots (QDs) have attracted widespread interest in biology and medicine. They are rapidly being used as new tools for both diagnostic and therapeutic purposes. Critical issues for further applications of QDs include the assessment of biocompatibility and biosafety of QDs. Most of previous researches concerning QD cytotoxicity focused on in vitro studies. In the present study, the impairments of acute exposure to well-modified and unmodified QDs (streptavidin-CdSe/ZnS and CdSe QDs, respectively) on synaptic transmission and plasticity were examined in adult rat hippocampal dentate gyrus (DG) area in vivo. The input/output (I/O) functions, paired-pulse ratio (PPR), field excitatory postsynaptic potential (fEPSP) and population spike (PS) amplitude were measured. The results showed that PPR and long-term potentiation (LTP) were all significantly decreased in these two types of QD-exposed rats compared to those in control rats. While the I/O functions and the amplitudes of fEPSP slope and PS amplitude of the baseline were significantly increased under QD exposure. These findings suggest that exposure to QDs, no matter whether they are well modified or not, could impair synaptic transmission and plasticity in the rat DG area in vivo and reveal the potential risks of QD applications in biology and medicine, especially in the toxin-susceptible central nervous system (CNS).

The exposure of bacteria to CdTe-core quantum dots: the importance of surface chemistryon cytotoxicity

A series of water-soluble CdTe-core quantum dots (QDs) with diameters below 5.0 nm andfunctionalized at their surface with polar ligands such as thioglycolic acid (TGA) or thetripeptide glutathione (GSH) were synthesized and characterized by UV–vis absorptionspectroscopy, their photoluminescence measurements, atomic force microscopy (AFM) andtransmission electron microscopy (TEM). Because cell elongations and growth inhibitionswere observed during labeling experiments, the cytotoxicity of CdTe-core QDs wasinvestigated. Using growth inhibition tests combining different bacterial strains withdifferent CdTe-core QDs, it was possible to demonstrate that the cytotoxicity ofQDs towards bacteria depends on exposure concentrations, surface chemistry andcoating, and that it varied with the strain considered. Growth inhibition testscarried out with heavy-metal-resistant bacteria, as well as ICP-AES analyses ofcadmium species released by CdTe@TGA QDs, demonstrated that the leakage ofCd2+ is notthe main source of QD toxicity. Our study suggests that QD cytotoxicity is rather due to the formationof TeO2 and probably the existence of CdO formed by surface oxidation. In this respect, QDspossessing a CdO shell appeared very toxic.

Biotinylated Glyco-Functionalized Quantum Dots: Synthesis, Characterization, and Cytotoxicity Studies

Quantum dots (QDs) containing surface carboxylic groups have been successfully modified using biotinylated glycopolymer and carbohydrate/biotin reagents via EDC coupling. The biotinylated glycopolymer was synthesized in controlled dimension via the reversible addition-fragmentation chain transfer (RAFT) polymerization of the three monomers containing biotin, sugar, and amine groups as pendent groups, respectively. The modified QDs were analyzed by dynamic light scattering and fluorescence spectrophotometry, and the data revealed no change in the physical properties of QDs after surface modification. Furthermore, the surface modified QDs showed excellent water solubility and colloidal stability. Subsequently, the availability of the biotin ligand on the surface of functionalized QDs was quantified using 4-hydroxyazobenzene 2-carboxylic acid (HABA)/avidin binding assay. Cell viability studies revealed that the cytotoxicity of QDs after surface functionalization is improved and that the biotinylated glycopolymer modified QDs showed an enhancement in biocompatibility as compared to that of the original QDs. The biotinylated glyco-functionalized quantum dots may act as new suitable fluorescent probes in biomedical applications.

UV-enhanced cytotoxicity of thiol-capped CdTe quantum dots in human pancreatic carcinoma cells

Quantum dots (QDs) have been gaining popularity due to their potential application in cellular imaging and diagnosis, but their cytotoxicity under light illumination has not been fully investigated. In this study, green and red mercaptopropionic acid capped CdTe quantum dots (MPA-CdTe QDs) were employed to investigate their cytotoxicity in human pancreatic carcinoma cells (PANC-1) under UV illumination. MPA-CdTe QDs exhibited excellent photostability under UV illumination and could be easily ingested by cells. The cytotoxicity of MPA-CdTe QDs was significantly enhanced under UV illumination, which was determined by changes in cell morphology as well as by decreases in the metabolic activity and cell counting. Our results indicated that green and red QDs had different cellular distribution and exhibited distinct UV-enhanced cytotoxicity. UV illumination enhanced the generation of reactive oxygen species (ROS) in cells containing QDs, and NAC antioxidant could reduce their damage to cells under UV illumination. Moreover, the influences of different UV illumination conditions on the viability of cells containing QDs were examined and discussed in detail.

Toxicity of CdTe Quantum Dots in Bacterial Strains

Contradictory results on quantum dot cytotoxicity exist for many types of biological systems, especially microorganisms. In this study, we compare the cytotoxicity of CdTe quantum dots (QDs) to four very different environmental bacterial strains, giving quantitative models of the growth curves for exposed organisms. The mechanisms of toxicity are explored by measuring reactive oxygen species generation by the QDs alone and investigating the oxidative damage to mutant bacteria especially sensitive to ROS. Electron microscopic examination also reveals factors that may contribute to resistance to nanoparticles in some strains.

The regulation of the gap junction of human mesenchymal stem cells through the internalization of quantum dots

The delivery mechanism of CdSe/ZnS quantum dots (QDs) into cells was previously found to critically determine the biocompatibility of QDs to human adult mesenchymal stem cells, but the associated mechanism remained unknown. The present study tried to establish a link between the above phenomenon and the change in gap junction upon QD internalization. By comparing Pep-1- and PolyFect-mediated QD internalizations, the connexin 43 (Cx43)-mediated gap junction intercellular communication (GJIC) of human adipose-derived adult stem cells was investigated in monolayer and in three-dimensional (3D) culture (alginate hollow spheres). The latter system offered cells more mobility, which was more similar as in vivo. The results showed that Pep-1-coated QDs, which escaped from the endo-/lysosome degradation, could activate the F-actin assembly and the ERK-dependent phosphorylation of Cx43. The consequence was a reduction in Cx43-mediated GJIC. When the cells were grown in high density 3D alginate hollow spheres instead of in monolayer, the decrease of GJIC caused by the QD internalization was restored. These results indicated that the adaptability in QDs-mediated regulation of GJIC with different delivery coatings depended on the culture systems. The study also suggested that the regulation of gap junction may play a key role in QD cytotoxicity.

The Cytotoxicity of Quantum Dots CdSe/CdS functionalized with -COOH and –NH2

AbstractRecently, semiconductor nanocrystals or quantum dots (QDs) aroused great concern because of their unique properties such as the size-dependent photoluminescence. They have many excellent applications in areas of molecular bioimaging, medical detection and even energy, especially as biosensing and imaging instead of fluorescent dyes. For the bio-safety, however, we should assess the cytotoxicity of QDs before used in biomedical imaging. Here, the cytotoxicity of amino-functionalized CdSe/CdS (CdSe/CdS-NH2) QDs and carboxy-functionalized CdSe/CdS (CdSe/CdS-COOH) QDs was investigated by MTT assay method. According to our findings, both CdSe/CdS-NH2 and CdSe/CdS-COOH have a dose-dependent effect on cell proliferation. The cytotoxicity of QDs varies with storing time of QDs and kinds of cells. The cytotoxicity of QDs modified with -COOH or -NH2 groups both vary with concentrations in positive linear or change with QD storing time in negative linear. The results indicate that CdSe/CdS-COOH QDs have lower toxicity than CdSe/CdS-NH2 QDs. Hela cell is somewhat more sensitive to amino- and carboxy-modified QDs than Bel7404 cell for MTT assays.

Targeting and imaging cancer cells by Folate-decorated, quantum dots (QDs)- loaded nanoparticles of biodegradable polymers

We developed a new strategy to prepare folate-decorated nanoparticles of biodegradable polymers for Quantum dots (QDs) formulation for targeted and sustained imaging for cancer diagnosis at its early stage. Poly(lactide)-vitamin E TPGS (PLA-TPGS) copolymer and vitamin E TPGS-carboxyl (TPGS-COOH) copolymer were synthesized. Their blend at various weight ratio was used to prepare folate-decorated nanoparticles (NPs) for QDs formulation to improve their imaging effects and reduce their side effects. The TPGS-COOH on the NP surface was designed to conjugate folate-NH 2 with advantage to make the targeting effect adjustable. The size of such NPs was found in the range of 280–300 nm. In vitro cellular uptakes of such NPs were investigated with confocal laser scanning microscopy (CLSM), which demonstrated much higher internalization of the folate-decorated QDs-loaded PLA-TPGS/TPGS-COOH NPs by MCF-7 breast cancer cells which are of over-expression of folate receptors than the cellular uptake by NIH 3T3 fibroblast cells which are of low expression of folate receptors. Compared with the free QDs, the QDs formulated in the PLA-TPGS/TPGS-COOH NPs showed lower in vitro cytotoxicity for both of MCF-7 cells and NIH 3T3 cells. Additionally, our findings indicated that under same conditions, cytotoxicity of QDs formulated in the PLA-TPGS/TPGS-COOH NPs is lower for normal cells such as NIH 3T3 cells than that for breast cancer such as MCF-7 breast cancer cells due to folate targeting effect. Targeted imaging by QDs formulated in folate-decorated PLA-TPGS/TPGS-COOH nanoparticles with better effects and less side effects is feasible.

The cytotoxicity of cadmium based, aqueous phase – Synthesized, quantum dots and its modulation by surface coating

In this report, we evaluated the cytotoxicity of a series of quantum dots (QDs) directly synthesized in aqueous phase, i.e., thiols-stabilized CdTe, CdTe/CdS core–shell structured and CdTe/CdS/ZnS core–shell–shell structured QDs, with a variety of cell lines including K562 and HEK293T. We have demonstrated that the CdTe QDs are highly toxic for cells due to the release of cadmium ions. Epitaxial growth of a CdS layer reduces the cytotoxicity of QDs to a small extent. However, the presence of a ZnS outlayer greatly improves the biocompatibility of QDs, with no observed cytotoxicity even at very high concentration and long-time exposure in cells. Our systematic investigation clearly shows that the cytotoxicity of QDs can be modulated through elaborate surface coatings and that the CdTe/CdS/ZnS core–shell–shell structured QDs directly synthesized in aqueous phase are highly promising biological fluorescent probes for cellular imaging.