CdTe Nanoparticles Display Tropism to Core Histones and Histone-Rich Cell Organelles

Department of Clinical Medicine, Trinity College Dublin, Dublin 2, Ireland.
Small (Impact Factor: 8.37). 11/2008; 4(11):2006-15. DOI: 10.1002/smll.200800088
Source: PubMed


The disclosure of the mechanisms of nanoparticle interaction with specific intracellular targets represents one of the key tasks in nanobiology. Unmodified luminescent semiconductor nanoparticles, or quantum dots (QDs), are capable of a strikingly rapid accumulation in the nuclei and nucleoli of living human cells, driven by processes of yet unknown nature. Here, it is hypothesized that such a strong tropism of QDs could be mediated by charge-related properties of the macromolecules presented in the nuclear compartments. As the complex microenvironment encountered by the QDs in the nuclei and nucleoli of live cells is primarily presented by proteins and other biopolymers, such as DNA and RNA, the model of human phagocytic cell line THP1, nuclear lysates, purified protein, and nucleic acid solutions is utilized to investigate the interactions of the QDs with these most abundant classes of intranuclear macromolecules. Using a combination of advanced technological approaches, including live cell confocal microscopy, fluorescent lifetime imaging (FLIM), spectroscopic methods, and zeta potential measurements, it is demonstrated that unmodified CdTe QDs preferentially bind to the positively charged core histone proteins as opposed to the DNA or RNA, resulting in a dramatic shift off the absorption band, and a red shift and decrease in the pholuminescence (PL) intensity of the QDs. FLIM imaging of the QDs demonstrates an increased formation of QD/protein aggregates in the presence of core histones, with a resulting significant reduction in the PL lifetime. FLIM technology for the first time reveals that the localization of negatively charged QDs to their ultimate nuclear and nucleolar destinations dramatically affects the QDs' photoluminescence lifetimes, and offers thereby a sensitive readout for physical interactions between QDs and their intracellular macromolecular targets. These findings strongly suggest that charge-mediated QD/histone interactions could provide the basis for QD nuclear localization downstream of intracellular transport mechanisms.

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    • "The emission wavelength is directly related to the particle size as larger particles will absorb lower energy, that is, longer wavelength photons [1]. Water-soluble CdTe-based QDs have attracted much interest in recent years for their potential applications in biological imaging especially, which consists in illuminating the cell membrane, the cytoplasm, or selected organelles using a fluorophore [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14]. Choosing an appropriate combination of staining agents enables one to elucidate cellular structures or mechanisms by visualising them with a fluorescence or confocal microscope. "
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    ABSTRACT: Water-soluble semiconducting nanocrystals or quantum dots (QDs) have attracted much interest in recent years due to their tuneable emission and potential applications in photonics and biological imaging. Fluorescence resonance energy transfer (FRET) processes are very important for elucidating biochemical mechanisms in vitro, and QDs constitute an excellent substrate for this purpose. In this work, new oligonucleotide-functionalised CdTe-based QDs were prepared, characterised and biologically tested. These QDs demonstrated interesting optical properties as well as remarkable in vitro behaviour and potential for a range of biological applications.
    Journal of Nanomaterials 09/2013; 2013(3):463951-(1-10). DOI:10.1155/2013/463951 · 1.64 Impact Factor
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    • "Differential miRNA expression may be consequences of epigenetic modification. The histone modification has been reported to be performed by cadmium telluride (CdTe) quantum dots (QDs) exposure131132. It suggests the possibility of involving miRNAs in the cytotoxicity of CdTe QDs. In addition, according to the non-genotoxic assessment, the apoptosis-like cell death is commonly induced by CdTe QDs in many cell lines133. "
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    ABSTRACT: MicroRNAs (miRNAs) are small 22-25 nucleotides long non-coding RNAs, that are conserved during evolution, and control gene expression in metazoan animals, plants, viruses, and bacteria primarily at post-transcriptional and transcriptional levels. MiRNAs ultimately regulate target gene expression by degrading the corresponding mRNA and/or inhibiting their translation. Currently, the critical functions of miRNAs have been established in regulating immune system, cell proliferation, differentiation and development, cancer and cell cycle by as yet unknown control mechanism. MiRNAs play an essential role in malignancy, and as tumour suppressors and oncogenes. Thus, discovery of new miRNAs will probably change the landscape of cancer genetics. Significantly different miRNA profiles can be assigned to various types of tumours, which could serve as phenotypic signatures for different cancers for their exploitation in cancer diagnostics, prognostics and therapeutics. If miRNA profiles can accurately predict malignancies, this technology could be exploited as a tool to surmount the diagnostic challenges. This review provides comprehensive and systematic information on miRNA biogenesis and their implications in human health.
    The Indian Journal of Medical Research 04/2013; 137(4):680-694. · 1.40 Impact Factor
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    • "Higher toxicity levels and apoptotic cell death was observed in this cell line with uncoated CdTe at 1 µg/ml [14]. Also, tropism to core histones and histone-rich organelles has been previously reported for CdTe-TGA QDs in macrophage THP1 cells [49]. This observation may explain in part the cellular toxicity of CdTe QDs and why apoptotic cell death is observed in some cases. "
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    ABSTRACT: Multiple applications of nanotechnology, especially those involving highly fluorescent nanoparticles (NPs) or quantum dots (QDs) have stimulated the research to develop simple, rapid and environmentally friendly protocols for synthesizing NPs exhibiting novel properties and increased biocompatibility. In this study, a simple protocol for the chemical synthesis of glutathione (GSH)-capped CdTe QDs (CdTe-GSH) resembling conditions found in biological systems is described. Using only CdCl2, K2TeO3 and GSH, highly fluorescent QDs were obtained under pH, temperature, buffer and oxygen conditions that allow microorganisms growth. These CdTe-GSH NPs displayed similar size, chemical composition, absorbance and fluorescence spectra and quantum yields as QDs synthesized using more complicated and expensive methods. CdTe QDs were not freely incorporated into eukaryotic cells thus favoring their biocompatibility and potential applications in biomedicine. In addition, NPs entry was facilitated by lipofectamine, resulting in intracellular fluorescence and a slight increase in cell death by necrosis. Toxicity of the as prepared CdTe QDs was lower than that observed with QDs produced by other chemical methods, probably as consequence of decreased levels of Cd+2 and higher amounts of GSH. We present here the simplest, fast and economical method for CdTe QDs synthesis described to date. Also, this biomimetic protocol favors NPs biocompatibility and helps to establish the basis for the development of new, “greener” methods to synthesize cadmium-containing QDs.
    PLoS ONE 01/2012; 7(1):e30741. DOI:10.1371/journal.pone.0030741 · 3.23 Impact Factor
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