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Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging
Published in
2010
PMID: 20023317
Volume: 21
   
Issue: 5
Abstract
Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters(Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin(BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid(FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ∼5.7% at pH 7.4 in phosphate buffer saline(PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy(XPS) suggests binding energies correlating to metal Au4f7/2∼83.97eV and Au4f5/2∼87.768eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ∼1nm and protein cluster aggregates of size ∼8nm. Photoluminescence studies show bright fluorescence with peak maximum at ∼674nm with the spectral profile covering the near-infrared(NIR) region, making it possible to image clusters at the 700-800nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500νgml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer. © IOP Publishing Ltd.
About the journal
JournalNanotechnology
ISSN09574484
Open AccessNo
Concepts (94)
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    Adenocarcinoma cells
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    AMIDE LINKAGES
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    ASCORBIC ACIDS
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    AU CLUSTERS
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    AU NANOCLUSTERS
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    Bio-conjugation
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    Bovine serum albumins
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    Cancer cells
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    Cancer detection
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    CANCER IMAGING
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    CANCER-TARGETING
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    CARCINOMA CELLS
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    Cell viability
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    CLUSTER INTERACTIONS
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    CONTROLLED REDUCTION
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    FLUORESCENCE EFFICIENCY
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    Folate receptor
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    FOLIC ACIDS
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    IMAGE CLUSTERS
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    In-vitro
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    Nanoconjugates
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    Near infrared
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    Near infrared region
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    NEGATIVE CONTROL
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    Peak maxima
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    PHOSPHATE BUFFER SALINES
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    Physicochemical property
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    PROTEIN CLUSTERS
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    REACTIVE OXYGEN
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    Serum albumin
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    SPECTRAL PROFILE
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    Squamous cell carcinoma
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    TARGETED IMAGING
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    TISSUE ABSORPTION
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    VITAMIN C
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    Amides
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    Atomic force microscopy
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    Binding energy
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    Body fluids
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    Cell culture
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    Chemical properties
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    Fluorescence
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    Infrared devices
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    Ketones
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    Light
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    Medical imaging
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    Nanoclusters
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    Organic acids
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    Oxygen
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    Proteins
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    Toxicity
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    Transmission electron microscopy
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    X ray photoelectron spectroscopy
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    Bovine serum albumin
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    Carrier protein
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    Cell surface receptor
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    Folate binding protein
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    Folate-binding protein
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    Folic acid
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    FORMAZAN
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    Gold
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    MTT FORMAZAN
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    Nanocomposite
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    Reactive oxygen metabolite
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    TETRAZOLIUM
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    Article
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    Cell line
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    Cell survival
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    Chemistry
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    Flow cytometry
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    Fluorescence microscopy
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    Human
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    Infrared spectroscopy
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    Luminescence
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    Metabolism
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    MOUTH TUMOR
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    Pathology
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    Tumor cell line
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    Carrier proteins
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    Cell line, tumor
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    FORMAZANS
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    Humans
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    LUMINESCENT MEASUREMENTS
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    Microscopy, atomic force
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    Microscopy, electron, transmission
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    Microscopy, fluorescence
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    MOUTH NEOPLASMS
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    Nanocomposites
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    Photoelectron spectroscopy
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    Reactive oxygen species
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    Receptors, cell surface
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    Serum albumin, bovine
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    Spectroscopy, fourier transform infrared
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    TETRAZOLIUM SALTS