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Use of quantum dots in the development of assays for cancer biomarkers

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Abstract

Biomarker assays may be useful for screening and diagnosis of cancer if a set of molecular markers can be quantified and statistically differentiated between cancerous cells and healthy cells. Markers of disease are often present at very low concentrations, so methods capable of low detection limits are required. Quantum dots (QDs) are nanoparticles that are emerging as promising probes for ultrasensitive detection of cancer biomarkers. QDs attached to antibodies, aptamers, oligonucleotides, or peptides can be used to target cancer markers. Their fluorescent properties have enabled QDs to be used as labels for in-vitro assays to quantify biomarkers, and they have been investigated as in-vivo imaging agents. QDs can be used as donors in assays involving fluorescence resonance energy transfer (FRET), or as acceptors in bioluminescence resonance energy transfer (BRET). The nanoparticles are also capable of electrochemical detection and are potentially useful for “lab-on-a-chip” applications. Recent developments in silicon QDs, non-blinking QDs, and QDs with reduced-size and controlled-valence further make these QDs bioanalytically attractive because of their low toxicity, biocompatibility, high quantum yields, and diverse surface modification flexibility. The potential of multiplexed sensing using QDs with different wavelengths of emission is promising for simultaneous detection of multiple biomarkers of disease.

Quantum dots have been conjugated to affinity probes to assay for cancer biomarkers including proteins, peptides, DNA, and whole cells

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Abbreviations

AFP:

α-Fetoprotein

BPDE:

Benzo[a]pyrene diol epoxide

BRET:

Bioluminescence resonance energy transfer

CA:

Cancer antigen

CEA:

Carcinoembryonic antigen

CK18:

Cytokeratin 18

DNA:

Deoxyribonucleic acid

ELISA:

Enzyme-linked immunosorbent assay

FRET:

Fluorescence resonance energy transfer

HER2:

Human epidermal growth factor receptor 2

IgG:

Immunoglobulin G

MMP:

Matrix metalloproteinase

MUC1:

Mucin 1

PCR:

Polymerase chain reaction

PEG:

Poly(ethylene glycol)

PSA:

Prostate-specific antigen

PSMA:

Prostate-specific membrane antigen

QD:

Quantum dot

RCA:

Rolling circle amplification

RNA:

Ribonucleic acid

SELEX:

Systematic evolution of ligands by exponential enrichment

uPA:

Urokinase-type plasminogen activator

VEGF:

Vascular endothelial growth factor

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Acknowledgements

The authors thank the Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, the Canada Research Chairs program, and Alberta Health and Wellness for their support. An Alberta Ingenuity Nanotechnology Scholarship (to MKW) and a China Scholarship Council visiting studentship (to JL) are also acknowledged.

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Wagner, M.K., Li, F., Li, J. et al. Use of quantum dots in the development of assays for cancer biomarkers. Anal Bioanal Chem 397, 3213–3224 (2010). https://doi.org/10.1007/s00216-010-3847-9

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  • DOI: https://doi.org/10.1007/s00216-010-3847-9

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