Quantum dots as phototoxic drugs and sensors of specific metabolic processes in living cells (original) (raw)
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Photophysics of dopamine-modified quantum dots and effects on biological systems
Nature Materials, 2006
Semiconductor quantum dots (QDs) have been widely used for fluorescent labelling. However, their ability to transfer electrons and holes to biomolecules leads to spectral changes and effects on living systems that have yet to be exploited. Here we report the first cell-based biosensor based on electron transfer between a small molecule (the neurotransmitter dopamine) and CdSe/ZnS QDs. QD-dopamine conjugates label living cells in a redox-sensitive pattern: under reducing conditions, fluorescence is only seen in the cell periphery and lysosomes. As the cell becomes more oxidizing, QD labelling appears in the perinuclear region, including in or on mitochondria. With the most-oxidizing cellular conditions, QD labelling throughout the cell is seen.
Quantum dots: synthesis, bioapplications, and toxicity
Nanoscale Research Letters, 2012
This review introduces quantum dots (QDs) and explores their properties, synthesis, applications, delivery systems in biology, and their toxicity. QDs are one of the first nanotechnologies to be integrated with the biological sciences and are widely anticipated to eventually find application in a number of commercial consumer and clinical products. They exhibit unique luminescence characteristics and electronic properties such as wide and continuous absorption spectra, narrow emission spectra, and high light stability. The application of QDs, as a new technology for biosystems, has been typically studied on mammalian cells. Due to the small structures of QDs, some physical properties such as optical and electron transport characteristics are quite different from those of the bulk materials.
Bioconjugate Chemistry, 2008
Chemical modification of the surface of CdSe/ZnS quantum dots (QDs) with small molecules or functional ligands often alters the characteristics of these particles. For instance, dopamine conjugation quenches the fluorescence of the QDs, which is a property that can be exploited for sensing applications if the conjugates are taken up into living cells. However, different sizes and/or preparations of mercaptocarboxylic acid solubilized QDs show very different properties when incubated with cells. It is unknown what physical parameters determine a QDs ability to interact with a cell surface, be endocytosed, escape from endosomes, and/or enter the nucleus. In this study, we examine the surface chemistry of QD-dopamine conjugates and present an optimized method for tracking the attachment of small biomolecules to the surface. It is found that the fluorescence intensity, surface charge, colloidal stability, and biological interactions of the QDs vary as a function of the density of dopamine on the surface. Successful targeting of QD-dopamine to dopamine receptor positive PC12 cells correlates with greater homogeneity of particle thiol layer, and a minimum number of ligands required for specific association can be estimated. These results will enable users to develop methods for screening QD conjugates for biological activity before proceeding to experiments with cell lines and animals.
Cellular uptake induced biotoxicity of surface-modified CdSe quantum dots
Journal of Nanoparticle Research, 2014
Cellular uptake of quantum dots (QDs) by cells is of utmost importance for establishing QDs as biostable fluorescent markers that facilitate early diagnosis and detection of cancer. The surface states of QDs are critical to enhance the cellular uptake. Biocompatible CDSe QDs were synthesized using mercaptopropionic acid, amino-ethanethiol HCl, cyltrimethylammonium bromide, dodecyltrimethylammonium bromide, tetrabutylammonium iodide (TBAI), and sodium dodecyl sulfate were functionalized using ligand-exchange method. Cytocompatibility and cellular uptake of QDs were evaluated in human embryonic kidney cells (HEK-29), and breast cancer cells (MCF-7) as reduced cytotoxicity is desirable for biological applications. Approximately, 60 % cytotoxicity was observed in all surface-coated QDs and QD100 in 72 h in both the cell lines, except TBAI that indicated 30 % cytotoxicity in 72 h, and only 10 % in 24 h. Glutathione, the detoxifying molecule, is detrimental for understanding the oxidative stress of the cell. The QDs showed enhanced Glutathione-S-transferase (GST) activity in the MCF-7 cell line. In HEK, CdSe per se was also able to induce a high level of GST. QDs toxicity may either be related to the induction of reactive oxygen species or the direct release of metal ions. Optimization of QDs in terms of quantification and DNA damage is imperative for realistic biological applications.
Quantum Dots and Their Interaction with Biological Systems
International Journal of Molecular Sciences
Quantum dots are nanocrystals with bright and tunable fluorescence. Due to their unique property, quantum dots are sought after for their potential in several applications in biomedical sciences as well as industrial use. However, concerns regarding QDs’ toxicity toward the environment and other biological systems have been rising rapidly in the past decade. In this mini-review, we summarize the most up-to-date details regarding quantum dots’ impacts, as well as QDs’ interaction with mammalian organisms, fungal organisms, and plants at the cellular, tissue, and organismal level. We also provide details about QDs’ cellular uptake and trafficking, and QDs’ general interactions with biological structures. In this mini-review, we aim to provide a better understanding of our current standing in the research of quantum dots, point out some knowledge gaps in the field, and provide hints for potential future research.
Labeling of subcellular redox potential with dopamine-conjugated quantum dots
2006
Semiconductor quantum dots (QDs) possess highly reactive electrons and holes after photoexcitation. The energy of these electrons and holes can be deliberately modulated by attaching the QD to an electron donor or acceptor. This eliminates (quenches) QD fluorescence, as well as affecting the ability of the QD to oxidize or reduce common biomolecules such as glutathione and DNA. This greatly alters the fluorescent properties and toxicity of such QDs inside cells. In this work, we show that a specific electron donor, the neurotransmitter dopamine, yields redox-sensitive conjugates when attached to at least some colors of CdSe/ZnS QDs. The potential for the use of such conjugates as sensors, and the implications for enhanced toxicity in such conjugates are discussed.
Nano Letters, 2004
Luminescent ZnO nanocrystals were synthesized by basic hydrolysis of Zn(OAc) 2 in the presence of oleic acid and then functionalized with (poly)aminotrimethoxysilanes in the presence of tetramethylammonium hydroxide to render the QDs water-dispersible. The highest photoluminescence quantum yield (17%) was achieved using N 1-(2-aminoethyl)-N 2-[3-(trimethoxysilyl)propyl]-1,2-ethanediamine as surface ligand. Transmission electron microscopy and powder x-ray diffraction showed highly crystalline materials with a ZnO nanoparticle diameter of about 4 nm. The cytotoxicity of the different siloxane-capped ZnO QDs towards growing Escherichia coli bacterial cells was evaluated in MOPS-minimal medium. Although concentrations of 5 mM in QDs caused a complete growth arrest in E. coli, siloxane-capped ZnO QDs appeared weakly toxic at lower doses (0.5 or 1 mM). The concentration of bioavailable Zn 2+ ions leaked from ZnO QDs was evaluated using the biosensor bacteria Cupriavidus metallidurans AE1433. The results obtained clearly demonstrate that concentrations of bioavailable Zn 2+ are too low to explain the inhibitory effects of the ZnO QDs against bacteria cells at 1 mM and that the siloxane shell prevents ZnO QDs from dissolution contrary to uncapped ZnO nanoparticles. Because of their low cytotoxicity, good biocompatibility, low cost and large number of functional amine end groups, which makes them easy to tailor for end-user purposes, siloxane-capped ZnO QDs offer a high potential as fluorescent probes and as biosensors.
Evaluation of Quantum Dot Cytotoxicity Based on Intracellular Uptake
Small, 2006
Advances in nanomaterials have led to promising candidates for many biological applications in research and medicine. Their novel physicochemical properties, attributable to their small size, chemical composition, surface structure, solubility, and shape, have been increasingly utilized in medicine for purposes of diagnosis, imaging, and drug delivery. Applications range from the fluorescent tracking of cells [1-3] and immunostaining assays [4] to magnetic resonance imaging. [5] Given the potential for widespread application and commercialization, nanomaterials will be increasingly uti-A C H T U N G T R E N N U N G lized for future biological applications. [6] Quantum dots (QDs) are an example of a nanomaterial that possesses optical properties ideal for biological imaging, which makes them a useful alternative to fluorescent dyes. The organic fluorophores currently used are vulnerable to chemical and metabolic degradation and are easily photobleached, which limits long-term cellular tracking. QDs offer advantages, such as bright photoluminescence, narrow emission, broad UV excitation, and high photostability, [7-9] to help overcome current optical-imaging limitations. Due to the tremendous focus on developing nanoparticles for imaging and therapeutic applications, there has been increasing interest in evaluating the toxicity of nanomaterials, [10] in particular, quantum dots. Some studies suggest that nanomaterials are not inherently benign and affect biological systems at the cellular, subcellular, and protein levels. [11-15] Akerman et al. demonstrated that some nanoparticulates are cleared from the circulation of live mice by the macrophages of the reticuloendothelial system in the liver and spleen. [16] Nevertheless, concerns have surfaced regarding the toxicity of QDs, in particular, those nanoparticles that are cadmium-containing and thus toxic to both cell cul
Differences in subcellular distribution and toxicity of green and red emitting CdTe quantum dots
Journal of Molecular Medicine-jmm, 2005
Quantum dots (QDs) are emerging as alternative or complementary tools to the organic fluorescent dyes currently used in bioimaging. QDs hold several advantages over conventional fluorescent dyes including greater photostability and a wider range of excitation/emission wavelengths. However, recent work suggests that QDs exert deleterious effects on cellular processes. This study examined the subcellular localization and toxicity of cadmium telluride (CdTe) QDs and pharmacological means of preventing QD-induced cell death. The localization of CdTe QDs was found to depend upon QD size. CdTe QDs exhibited marked cytotoxicity in PC12 and N9 cells at concentrations as low as 10 µg/ml in chronic treatment paradigms. QD-induced cell death was characterized by chromatin condensation and membrane blebbing and was more pronounced with small (2r=2.2±0.1 nm), green emitting positively charged QDs than large (2r=5.2±0.1 nm), equally charged red emitting QDs. Pretreatment of cells with the antioxidant N-acetylcysteine and with bovine serum albumin, but not Trolox, significantly reduced the QD-induced cell death. These findings suggest that the size of QDs contributes to their subcellular distribution and that drugs can alter QD-induced cytotoxicity.
Physiological behavior of quantum dots
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 2012
Quantum dots (QDs) have shown great potentials in biomedical applications like bioimaging, sensors and diagnostics due to various advantages such as their robust fluorescence, remarkable photostability, large absorption cross section, and tunable fluorescence emission. The fate, behavior, metabolism, and toxicities of QDs are the primary aspects to be assessed before their bio-applications. Numerous studies concerning those aspects have been reported in the past years. However, only several reviews discussed the toxicities of QDs and various contradictory conclusions appear between these studies. In this review, the fate, metabolism, and behaviors of various QDs and crucial parameters that may determine their fate and behavior in vivo are discussed in depth. This review may provide insights for a better understanding of the biological impacts of QDs. We also propose several suggestions for how to develop QDs application in humans in the future.