Assessment of cytotoxicity of quantum dots and gold nanoparticles using cell-based impedance spectroscopy

A continuous online technique based on electric cell-substrate impedance sensing (ECIS) was demonstrated for measuring the concentration and time response function of fibroblastic V79 cells exposed to nanomaterials such as quantum dots (QDs) and fluorescent gold nanoparticles. The half-inhibition concentration, (ECIS50), the required concentration to attain 50% inhibition of the cytotoxic response, was estimated from the response function to ascertain cytotoxicity during the course of measurement. The ECIS50 values agreed well with the results obtained using the standard neutral red assay. Cadmium selenide quantum dots showed direct cytotoxicity with the ECIS assay. For the cadmium telluride quantum dots, significant toxicity could be assigned to free cadmium, although additional toxicity could be attributed to the QDs per se. The QDs synthesized with indium gallium phosphide and the fluorescent gold nanoparticles were not cytotoxic.     

Biocompatible fluorescence-enhanced ZrO₂-CdTe quantum dot nanocomposite for in vitro cell imaging

With advances of quantum dots (QDs) in bioimaging applications, various materials have been used to coat QDs to reduce their nanotoxicity; however, the coating could introduce new toxic sources and quench the fluorescence in bioimaging applications. In this work, ZrO?, an excellent ceramic material with low extinction coefficient and good biocompatibility, is utilized to coat CdTe QDs for the first time. Experimental results show that ZrO?-QD nanocomposites with the size of ~30 nm possess enhanced fluorescence emission, lower nanotoxicity and gradually increased fluorescence under 350 nm light illumination. After functionalization with folic acid, they were applied to label cultured HeLa cells effectively. Therefore, the ZrO?-QD nanocomposites could be promising biocompatible nanomaterials with strong fluorescence emission to replace or complement QDs in biomedical applications.     

Toxicity of CdTe Quantum Dots on Yeast Saccharomyces Cerevisiae

Along with the widespread development of their bioapplications, concerns about the biosafety of quantum dots (QDs) have increasingly attracted intensive attention. This study examines the toxic effect and subcellular location of cadmium telluride (CdTe) QDs with different sizes against yeast Saccharomyces cerevisiae. The innovative approach is based on the combination of microcalorimetric, spectroscopic, electrochemical, and microscopic methods, which allows analysis of the toxic effect of CdTe QDs on S. cerevisiae and its mechanism. According to the values of the half inhibitory concentration (IC(50) ), CdTe QDs exhibit marked cytotoxicity in yeast cells at concentrations as low as 80.81 nmol L(-1) for green-emitting CdTe QDs and 17.07 nmol L(-1) for orange-emitting CdTe QDs. QD-induced cell death is characterized by cell wall breakage and cytoplasm blebbing. These findings suggest that QDs with sizes ranging from 4.1 to 5.8 nm can be internalized into yeast cells, which then leads to QD-induced cytotoxicity. These studies provide valuable information for the design and development of aqueous QDs for biological applications.     

Cytotoxicity tests of water soluble ZnS and CdS quantum dots

Cytotoxicity tests of zinc sulfide (ZnS) and cadmium sulfide (CdS) quantum dots (QDs) synthesized via all-aqueous process with various surface conditions were carried out with human endothelial cells (EA hy926) using two independent viability assays, i.e., by cell counting following Trypan blue staining and by measuring Alamar Blue (AB) fluorescence. The ZnS QDs with all four distinct types of surface conditions were nontoxic at both 1 microM and 10 microM concentrations for at least 6 days. On the other hand, the CdS QDs were nontoxic only at 1 microM, and showed significant cytotoxicity at 10 microM after 3 days in the cell counting assay and after 4 days in the AB fluorescence assay. The CdS QDs with (3-mercaptopropyl)trimethoxysilane (MPS)-replacement plus silica capping were less cytotoxic than those with 3-mercaptopropionic acid (MPA) capping and those with MPS-replacement capping. Comparing the results of ZnS and CdS QDs with the same particle size, surface condition and concentration, it is indicated that the cytotoxicity of CdS QDs and the lack of it in ZnS QDs were probably due to the presence and absence of the toxic Cd element, respectively. The nontoxicity of the aqueous ZnS QDs makes them favorable for in vivo imaging applications.     

Extracellular biosynthesis of biocompatible CdSe quantum dots

An extracellular biosynthesis method has been developed to prepare cadmium selenide (CdSe) quantum dots (QDs) with strong fluorescence emission by incubating cheap Cd and Se inorganic salts with Escherichia coli (E.coli) bacteria. Ultraviolet–visible absorption spectra, photoluminescence (PL) spectra, and high‐resolution transmission electron microscopy analysis showed that the biosynthesised CdSe QDs have an average size of 3.1 nm, the excellent optical properties with fluorescence emission around 494 nm, and the good crystallinity. It was found that addition of 80 mg of mercaptosuccinic acid resulted in the formation of CdSe QDs with highest PL intensity. Furthermore, Fourier‐transform infrared spectra of as‐synthesised CdSe QDs confirmed the presence of a surface protein capping layer. The biosynthesised CdSe QDs were incorporated into the yeast cells as illustrated by laser confocal scanning microscopy images, showing a great potential in bio‐imaging and bio‐labelling application.Inspec keywords: microorganisms, molecular biophysics, fluorescence, visible spectra, nanofabrication, nanobiotechnology, proteins, cellular biophysics, nanostructured materials, wide band gap semiconductors, cadmium compounds, semiconductor quantum dots, II‐VI semiconductors, transmission electron microscopy, photoluminescence, optical microscopy, ultraviolet spectra, Fourier transform infrared spectra, biological techniques, semiconductor growthOther keywords: biocompatible CdSe quantum dots, extracellular biosynthesis method, cadmium selenide quantum dots, high‐resolution transmission electron microscopy analysis, biosynthesised CdSe QDs, Fourier‐transform infrared spectra, Escherichia coli, ultraviolet‐visible absorption spectra, PL intensity, fluorescence emission, photoluminescence spectra, optical properties, surface protein capping layer, laser confocal scanning microscopy images, bioimaging, biolabelling application, yeast cells, f mercaptosuccinic acid, CdSe     

A pilot study in non-human primates shows no adverse response to intravenous injection of quantum dots

Quantum dots have been used in biomedical research for imaging, diagnostics and sensing purposes. However, concerns over the cytotoxicity of their heavy metal constituents and conflicting results from in vitro and small animal toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90?days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90?days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates.     

Photoluminescent silicon quantum dots in core/shell configuration: synthesis by low temperature and spontaneous plasma processing

Quantum confinement in zero-dimensional silicon nanocrystals (nC) in the quantum dot (QD) configuration has triggered a tremendous interest in nanostructured device technology. However, the formation of Si-QDs eventually proceeds through multi-step routes and involves high temperature processing that impedes preferred device configuration. The present work demonstrates the formation of nC-Si QDs of controlled size, density and distribution through one-step and spontaneous plasma processing, at a low substrate temperature (300?°C) compatible for device fabrication. Direct growth of nC-Si/SiO(x) core/shell quantum dots embedded in the a-Si matrix, 6.4-3.7 nm in diameter and with number density in the range ～ 6 × 10(9)-1 × 10(11) cm(-2) has been accomplished, following a novel route where He dilution to SiH(4) in RF plasma CVD has been found instrumental. On gradual reduction in the size of QDs, splitting of the energy bands widens the optical band gap and induces visible photoluminescence that appears controllable by tuning the size and density of the dots. This low temperature and spontaneous plasma processing of nC-Si/SiO(x) core/shell QDs that exhibit the quantum size effect in photoluminescence is being reported for the first time.     

Microcalorimetric, spectroscopic and microscopic investigation on the toxic effects of CdTe quantum dots on Halobacterium halobium R1

The biological effect of CdTe quantum dots (QDs) on Halobacterium halobium R1 (H. halobium R1) growth was analyzed by a microcalorimetric technique. By using a TAM air eight channels microcalorimeter, the thermogenic curves of H. halobium R1 growth were obtained at 37?°C. To analyze the results, the maximum heat power (P(m)) and the growth rate constants (k) were determined, which showed that they were correlated to the concentration of QDs. The addition of quantum dots caused a gradual increase of P(m) and k at low concentrations of QDs, and a conspicuous decrease at high concentrations. For confirmation, the turbidity (OD(600)) and respiratory rate at different concentrations of QDs were studied. The morphology of H. halobium R1 cells both in the absence and presence of QDs was examined by transmission electron microscopy (TEM). The results of these studies were corroborated with ones derived from microcalorimetry. In this work, the mechanism of cytotoxicity of QDs was explored through fluorescence spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS) and microcalorimetry. It was clear that metabolic mechanism of H. halobium R1 growth was changed by the addition of QDs. To the best of our knowledge, the thermokinetics and toxicology of CdTe QDs against H. halobium R1 were obtained for the first time by microcalorimetry.     

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.      

Freestanding silicon quantum dots: origin of red and blue luminescence

In this paper, we studied the behavior of silicon quantum dots (Si-QDs) after etching and surface oxidation by means of photoluminescence (PL) measurements, Fourier transform infrared spectroscopy (FTIR) and electron paramagnetic resonance spectroscopy (EPR). We observed that etching of red luminescing Si-QDs with HF acid drastically reduces the concentration of defects and significantly enhances their PL intensity together with a small shift in the emission spectrum. Additionally, we observed the emergence of blue luminescence from Si-QDs during the re-oxidation of freshly etched particles. Our results indicate that the red emission is related to the quantum confinement effect, while the blue emission from Si-QDs is related to defect states at the newly formed silicon oxide surface.     

量子点/碳复合材料在碱金属离子电池的应用进展EI北大核心

碱金属离子电池作为可充电电池,是目前重要的储能设备之一。它凭借能量密度大、工作电压高、无“记忆效应”、自放电小、绿色无污染等优点在近些年来受到人们的广泛关注。电极材料是影响碱金属离子电池电化学性能的重要因素之一,因此,寻求比容量高、结构稳定的电极材料是推动碱金属离子电池发展的关键。量子点/碳复合材料(QDs/C)集合量子点与碳材料的优势,是碱金属离子电池优异的候选电极材料。本文首先对量子点进行简要介绍,然后分别综述单质量子点/碳复合材料、化合物量子点/碳复合材料及异质结构量子点/碳复合材料在碱金属离子电池中的应用进展。最后,分析量子点/碳复合材料作为碱金属离子电池电极材料的优势与不足,针对目前存在的问题提出了未来发展的方向:(1)探索新型方法,解决量子点及其复合材料的团聚问题;(2)研究SEI膜的结构性能等,解决首次库仑效率偏低的问题;(3)明确反应机理,获取更优异的电化学性能。     

'Green'-synthesized near-infrared PbS quantum dots with silica-PEG dual-layer coating: ultrastable and biocompatible optical probes for in vivo animal imaging

In this paper, PbS semiconductor quantum dots (QDs) with near-infrared (NIR) photoluminescence were synthesized in oleic acid and paraffin liquid mixture by using an easily handled and 'green' approach. Surface functionalization of the QDs was accomplished with a silica and polyethylene glycol (PEG) phospholipid dual-layer coating and the excellent chemical stability of the nanoparticles is demonstrated. We then successfully applied the ultrastable PbS QDs to in vivo sentinel lymph node (SLN) mapping of mice. Histological analyses were also carried out to ensure that the intravenously injected nanoparticles did not produce any toxicity to the organism of mice. These experimental results suggested that our ultrastable NIR PbS QDs can serve as biocompatible and efficient probes for in vivo optical bioimaging and has great potentials for disease diagnosis and clinical therapies in the future.     

碳量子点的生物应用:成像、载药与毒性

碳量子点作为一种新型的纳米材料,具有荧光性能优异、尺寸小、毒性低等诸多优势,因而具有良好的应用前景,尤其在生物医学领域有突出的应用价值,近年来引起了科研者们的广泛关注。在介绍碳量子点光学性质的基础上,重点综述了碳量子点在生物成像、诊疗剂应用及碳量子点生物毒性等方面的最新研究进展,并探讨了碳量子点未来的发展方向和前景。     

水溶性Cu∶CdTe/CdS核壳量子点的合成、表征及细胞毒性检测

采用水相法合成了Cu掺杂CdTe量子点,并用CdS壳层进行包覆,得到了Cu∶CdTe/CdS核壳结构量子点。采用荧光发射光谱(FL)、紫外可见吸收光谱(UV-Vis)、透射电镜(TEM)以及能谱仪(EDS)等手段对CdTe量子点和Cu∶CdTe/CdS核壳量子点进行了表征。研究了不同Cu掺杂浓度、CdS壳层生长时间以及Cd/硫脲物质的量比对Cu∶CdTe掺杂量子点光学性能的影响,并采用人成骨肉瘤细胞(MG-63细胞)对样品做了细胞毒性分析。研究结果表明:通过掺杂和包壳的步骤,合成的Cu∶CdTe/CdS核壳量子点在CdTe量子点的基础上实现了荧光发射红移,荧光强度提高,以及细胞毒性降低。     

Tissue and species differences in the application of quantum dots as probes for biomolecular targets in the inner ear and kidney

Quantum dots (QDs) are useful biological probes because of the increased photostability and quantum efficiency they offer over organic fluorophores. However, toxicity concerns arise because the QD core is composed of cadmium and selenium, metals known to be unsafe for humans and animals. We investigated the feasibility of quantum dots as biological labels for imaging studies of inner ear and kidney, tissues that share a polarized epithelial arrangement and drug susceptibility. We found that methods for labeling the actin cytoskeleton of monolayers of cultured amphibian kidney cells (Xenopus A6) with 565 nm QD conjugates were not feasible with large Xenopus inner ear organs. We then compared the uptake of 565 nm cationic peptide-targeted and nontargeted QDs in live kidney cell lines (amphibian, A6 and XLK-WG; human, HEK-293). Results showed that targeted QDs are internalized by all three kidney cell lines, and that nontargeted CdSe nanocrystals are sequestered only by human kidney cells. CellTracker Red CMTPX confirmed the membrane integrity and viability of HEK-293 cells that internalized QDs. Our results demonstrate species and tissue differences in QD uptake and labeling, and underscore the need for long-term studies of QD toxicity and fate in cells     

Quantum dots for human mesenchymal stem cells labeling. A size-dependent autophagy activation

Lately certain cytotoxicity of quantum dots (QDs) and some deleterious effects of labeling procedure on stem cells differentiation abilities were shown. In the present study we compared cytotoxicity and intracellular processing of two different-sized protein-conjugated QDs after labeling of the human mesenchymal stem cells (hMSC). An asymmetrical intracellular uptake of red (605 nm) and green (525 nm) quantum dots was observed. We describe for the first time a size-dependent activation of autophagy, caused by nanoparticles.     

UV-enhanced toxicity of water-stable quantum dots in human pancreatic carcinoma cells

Zn-based (capped with thioglycolic acid (TGA) or 3-mercaptopropionic acid (MPA)) and Cd-based quantum dots (QDs) (capped with TGA or L-glutathione), were synthesised and used to investigate their cytotoxicity to human pancreatic carcinoma cells (PANC-1) in absence and presence of UV irradiation. Zn-based QDs exhibited less intrinsic cytotoxicity than the Cd-based QDs, however, the excitation of 50?µg/mL-QDs using UV lamp significantly enhanced the cytotoxicity of both QDs. After 15?min of UV irradiation, the viability for cells exposed to Cd-based QDs capped with TGA or glutathione was 49%?±?6% or 56%?±?3%, respectively. The corresponding cell viability in the control test was 83%?±?8% after 15?min of UV irradiation. In turn, the viability for cells exposed to Zn-based QDs capped with 3-MPA or TGA was 64%?±?3% and 52%?±?3%, respectively, after 30?min of UV irradiation; the cell viability in the control test was 80%?±?7% for the same UV irradiation time. Laser scanning confocal analyses evidenced that QDs can be easily ingested by PANC-1. Based on their good compositional stability, Zn-based QDs capped with 3-MPA can be considered a promising material for nanomedicine applications until concentrations of 200?µg/mL.     

Aqueous‐Phase Synthesis of Highly Luminescent CdTe/ZnTe Core/Shell Quantum Dots Optimized for Targeted Bioimaging

Semiconductor quantum dots (QDs) have traditionally been synthesized in organic phase and transferred to aqueous solution by functionalizing their surface with silica, polymers, short‐chain thiol ligand, or phospholipid micelles. However, these complex steps result in i) a reduction of the quantum yield (QY) of QDs, ii) partial degrdation of the QDs, and iii) a drastic increase in the hydrodynamic size of QDs, which may hinder their biomedical applications. In this work, the fabrication and applications of cysteine‐capped CdTe/ZnTe QDs, which are directly synthesized in aqueous media, as optical probes for specific targeting of pancreatic and esophageal cancer cells in vitro are reported, as well as their capability for in vivo imaging. The CdTe/ZnTe QDs are synthesized in a one‐pot method and capped with amino acid cysteine, which contains both carboxyl and amine functional groups on their surfaces for bioconjugation. The fabricated QDs have an ultrasmall hydrodynamic diameter (3–5 nm), possess high QY (52%), and are non‐toxic to cells at experimental dosages. Confocal imaging is used to demonstrate a receptor‐mediated uptake of antibody‐conjugated QDs into pancreatic cancer cells in vitro. In vitro cytotoxicity studies (MTS‐assay) show that the IC₅₀ value of these QDs is ≈160 µg mL^?1, demonstrating low toxicity. In addition, the QDs are used for small‐animal imaging where the in vivo biocompatiblity of these QDs and their clearance following systemic injection is studied.     

CdTe quantum dots accelerate the speed of Pfu-based polymerase chain reaction

It has not been previously reported that the speed of polymerase chain reaction (PCR) can be accelerated by quantum dots (QDs). In the present work, the addition of cadmium telluride (CdTe) QDs resulted in significant time-saving compared with the conventional PCR. The reaction time could be significantly shortened from 143 to 46 min without compromising the general efficiency in a PCR. CdTe QD-facilitated fast PCR also displayed excellent hot-start effects.     

Bioactivity of the conjugation of green-emitting CdTe quantum dots with a carborane complex

In this report, we describe the effect of conjugating o-carborane-C(1)C(2)-dicarboxylic acid (o-C2B10H10-C2O4H2, denoted as Cbac2) to cadmium telluride quantum dots (CdTe QDs) capped with cysteamine on the photophysics and cytotoxicity of the QDs. Cbac2 quenches the fluorescence intensity and induces a red shift of the fluorescence emission peak. Meanwhile, studies with a real time cell electronic sensing (RT-CES) system and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay indicate that the combination of the carborane carboxylic acid derivative Cbac2 with relevant QDs can efficiently improve the inhibition efficiency for target cancer cells when compared with a single ligand or the CdTe QDs alone. This study raises the possibility for the labeling of the important pharmacophore with QDs and the design of new promising anticancer agents containing the carborane pharmacophores for cancer therapy.