Use of fluorescent quantum dot bioconjugates for cellular imaging of immune cells, cell organelle labeling, and nanomedicine: surface modification regulates biological function, including cytotoxicity (original) (raw)
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Nano Letters, 2004
Nanocrystal quantum dots (QDs) have been applied to molecular biology because of their greater and longer fluorescence. Here we report the potential cytotoxicity of our characterized QDs modified with various molecules. Surface modification of QDs changed their physicochemical properties. In addition, the cytotoxicity of QDs was dependent on their surface molecules. These results suggested that the properties of QDs are not related to those of QD-core materials but to molecules covering the surface of QDs.
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
Evaluation of Toxicity and Gene Expression Changes Triggered by Quantum Dots
Bulletin of The Korean Chemical Society, 2010
Quantum dots (QDs) are extensively employed for biomedical research as a fluorescence reporter and their use for various labeling applications will continue to increase as they are preferred over conventional labeling methods for various reasons. However, concerns have been raised over the toxicity of these particles in the biological system. Till date no thorough investigation has been carried out to identify the molecular signatures of QD mediated toxicity. In this study we evaluated the toxicity of CdSe, Cd1-xZnxS/ZnS and CdSe/ZnS quantum dots having different spectral properties (red, blue, green) using human embryonic kidney fibroblast cells (HEK293). Cell viability assay for both short and long duration exposure show concentration material dependent toxicity, in the order of CdSe > Cd1-xZnxS/ ZnS > CdSe/ZnS. Genome wide changes in the expression of genes upon QD exposure was also analyzed by wholegenome microarray. All the three QDs show increase in the expression of genes related to apoptosis, inflammation and response towards stress and wounding. Further comparison of coated versus uncoated CdSe QD-mediated cell death and molecular changes suggests that ZnS coating could reduce QD mediated cytotoxicity to some extent only.
Bioconjugate Chemistry
Interest in taking advantage of the unique spectral properties of semiconductor quantum dots (QDs) has driven their widespread use in biological applications such as in vitro cellular labeling/imaging and sensing. Despite their demonstrated utility, concerns over the potential toxic effects of QD core materials on cellular proliferation and homeostasis have persisted, leaving in question the suitability of QDs as alternatives for more traditional fluorescent materials (e.g., organic dyes, fluorescent proteins) for in vitro cellular applications. Surprisingly, direct comparative studies examining the cytotoxic potential of QDs versus these more traditional cellular labeling fluorophores remain limited. Here, using CdSe/ZnS (core/shell) QDs as a prototypical assay material, we present a comprehensive study in which we characterize the influence of QD dose (concentration and incubation time), QD surface capping ligand and delivery modality (peptide or cationic amphiphile transfection r...
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.
The cytotoxic effects of polymer-coated quantum dots and restrictions for live cell applications
Biomaterials, 2012
The interest in the biomedical use of highly fluorescent and photostable nanoparticles such as quantum dots (QDots) is vastly increasing. One major hurdle that impedes QDot use in live cells and animals is their potential toxicity. Here, we employ a recently described multiparametric setup to determine the concentration at which common polymer-coated QDots become non-cytotoxic. We found that toxic effects are strongly related to the intracellular QDot amount that can be controlled by their specific surface coating. Using lysosomal buffer systems and proliferation-restricted cells, intracellular QDots were found to localize in endosomes, where they generate reactive oxygen species, interfere with cell cytoskeleton and leach free Cd 2+ ions due to QDot dissolution, resulting in increased toxicity and impeded QDot fluorescence. Furthermore, we find that asymmetric partitioning of QDots upon recurrent cell division results in the sacrifice of heavily-loaded cells and a rapid loss of particles in live cells, limiting the use of currently available QDots for long-term imaging and defining the non-cytotoxic concentration as 10-fold lower than commonly used concentrations.
Journal of Nanobiotechnology, 2010
Background: The unique and tuneable photonic properties of Quantum Dots (QDs) have made them potentially useful tools for imaging biological entities. However, QDs though attractive diagnostic and therapeutic tools, have a major disadvantage due to their inherent cytotoxic nature. The cellular interaction, uptake and resultant toxic influence of CdTe QDs (gelatinised and non-gelatinised Thioglycolic acid (TGA) capped) have been investigated with pheochromocytoma 12 (PC12) cells. In conjunction to their analysis by confocal microscopy, the QD -cell interplay was explored as the QD concentrations were varied over extended (up to 72 hours) co-incubation times. Coupled to this investigation, cell viability, DNA quantification and cell proliferation assays were also performed to compare and contrast the various factors leading to cell stress and ultimately death.