Skip to main content

Functionalized Gold Nanoparticles for Detection of Cancer Biomarkers

  • Living reference work entry
  • First Online:
General Methods in Biomarker Research and their Applications

Abstract

Biomarkers are molecular indicators that represent the biological status of health and disease. In human cancers, proteins, nucleic acids, and small molecules can be used as biomarkers for detection and assessment. Molecular data measured using biomarkers can provide insight into a tumor’s genotype or phenotype and aid in diagnosis and prognosis of cancer. The physical, chemical, and optical qualities of gold surfaces form the basis for much of their use as biomarker detection platforms. Functionalized gold nanoparticles (AuNP) are the most prevalent gold surface biomarker detection platform, and a majority of functionalization strategies have been applied to AuNP surfaces. This review focuses on recent and compelling developments in the functionalization of AuNP surfaces for the detection of biomarkers associated with human cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

Abbreviations

ABTS:

2,2′-Azino-bis(3-Ethylbenzothiazoline-6-Sulfonic Acid)

AFP:

α-Fetoprotein

ALP:

Alkaline Phosphatase

ANG:

Angiogenin

APP:

4-Aminophenylphosphate

Au-MNC:

Gold-Coated Magnetic Nanoparticle Cluster

AuNP:

Gold Nanoparticle

BHb:

Bovine Hemoglobin

BPA:

Bisphenol A

BSA:

Bovine Serum Albumin

DABCYL:

4-((4′-(Dimethyl-amino)phenyl)azo)benzoic Acid

DIC:

Differential Interference Contrast

DLS:

Dynamic Light Scattering

DMSO:

Dimethyl Sulfoxide

dsDNA:

Double-Stranded DNA

DTT:

Dithiothreitol

ELISA:

Enzyme-Linked Immunosorbent Assay

FITC:

Fluorescein Isothiocyanate

GAPDH:

Glyceraldehyde 3-Phosphate Dehydrogenase

hAuNP:

Hairpin DNA Gold Nanoparticle

HAV:

Hepatitis A Virus

HBV:

Hepatitis B Virus

HCV:

Hepatitis C Virus

HER2:

Human Epidermal Growth Factor Receptor 2

HIV:

Human Immunodeficiency Virus

HRP:

Horseradish Peroxidase

IPCR:

Immuno-PCR

MB:

Molecular Beacon

MIP:

Molecularly Imprinted Polymer

MIP-NP:

Molecularly Imprinted Polymer Nanoparticle

miRNA:

MicroRNA

MMP:

Magnetic Microparticle

NIP-NP:

Non-imprinted Polymer Nanoparticle

NP:

Nanoparticle

PCR:

Polymerase Chain Reaction

PFU:

Plaque-Forming Unit

PSA:

Prostate-Specific Antigen

qPCR:

Quantitative Polymerase Chain Reaction

qRT-PCR:

Quantitative Reverse Transcription Polymerase Chain Reaction

RSV:

Respiratory Syncytial Virus

SELEX:

Systematic Evolution of Ligands by Exponential Enrichment

SERS:

Surface-Enhanced Raman Scattering

SNP:

Single Nucleotide Polymorphism

SPR:

Surface Plasmon Resonance

ssDNA:

Single-Stranded DNA

TEM:

Transmission Electron Microscope

TPS:

Two-Photon Scattering

References

  • Adams NM, Jackson SR, Haselton FR, Wright DW. Design, synthesis, and characterization of nucleic-acid-functionalized gold surfaces for biomarker detection. Langmuir. 2012;28(2):1068–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Alhasan AH, Kim DY, Daniel WL, Watson E, Meeks JJ, Thaxton CS, Mirkin CA. Scanometric microRNA array profiling of prostate cancer markers using spherical nucleic acid–gold nanoparticle conjugates. Anal Chem. 2012;84(9):4153–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Boder ET, Midelfort KS, Wittrup KD. Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc Natl Acad Sci. 2000;97(20):10701–5.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cao YC, Jin R, Mirkin CA. Nanoparticles with Raman spectroscopic fingerprints for DNA and RNA detection. Science. 2002;297(5586):1536–40.

    Article  CAS  PubMed  Google Scholar 

  • Chun C, Joo J, Kwon D, Kim CS, Cha HJ, Chung M-S, Jeon S. A facile and sensitive immunoassay for the detection of alpha-fetoprotein using gold-coated magnetic nanoparticle clusters and dynamic light scattering. Chem Commun. 2011;47(39):11047–9.

    Article  CAS  Google Scholar 

  • Cissell KA, Shrestha S, Deo SK. MicroRNA detection: challenges for the analytical chemist. Anal Chem. 2007;79(13):4754–61.

    Article  CAS  Google Scholar 

  • Conde J, de la Fuente J, Baptista P. RNA quantification using gold nanoprobes – application to cancer diagnostics. J Nanobiotechnol. 2010;8(1):5.

    Article  Google Scholar 

  • DeRisi J, Penland L, Brown PO, Bittner ML, Meltzer PS, Ray M, Chen Y, Su YA, Trent JM. Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet. 1996;14(4):457–60.

    Article  CAS  PubMed  Google Scholar 

  • Dubertret B, Calame M, Libchaber AJ. Single-mismatch detection using gold-quenched fluorescent oligonucleotides. Nat Biotechnol. 2001;19(4):365.

    Article  CAS  PubMed  Google Scholar 

  • Elghanian R, Storhoff JJ, Mucic RC, Letsinger RL, Mirkin CA. Selective colorimetric detection of polynucleotides based on the distance-dependent optical properties of gold nanoparticles. Science. 1997;277(5329):1078–81.

    Article  CAS  PubMed  Google Scholar 

  • Fan C, Wang S, Hong JW, Bazan GC, Plaxco KW, Heeger AJ. Beyond superquenching: hyper-efficient energy transfer from conjugated polymers to gold nanoparticles. Proc Natl Acad Sci. 2003;100(11):6297–301.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Harry SR, Hicks DJ, Amiri KI, Wright DW. Hairpin DNA coated gold nanoparticles as intracellular mRNA probes for the detection of tyrosinase gene expression in melanoma cells. Chem Commun. 2010;46(30):5557–9.

    Article  CAS  Google Scholar 

  • Hill HD, Mirkin CA. The bio-barcode assay for the detection of protein and nucleic acid targets using DTT-induced ligand exchange. Nat Protoc. 2006;1(1):324–36.

    Article  CAS  PubMed  Google Scholar 

  • Hu R, Fu T, Zhang X-B, Kong R-M, Qiu L-P, Liu Y-R, Liang X-T, Tan W, Shen G-L, Yu R-Q. A proximity-dependent surface hybridization strategy for constructing an efficient signal-on electrochemical DNAzyme sensing system. Chem Commun. 2012;48(76):9507–9.

    Article  CAS  Google Scholar 

  • Huang Z, Lin L, Gao Y, Chen Y, Yan X, Xing J, Hang W. Bladder cancer determination via two urinary metabolites: a biomarker pattern approach. Mol Cell Proteomics. 2011;10(10):M111.007922.

    Article  PubMed Central  PubMed  Google Scholar 

  • Iorio MV, Croce CM. MicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 2012;4(3):143–59.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jayagopal A, Halfpenny KC, Perez JW, Wright DW. Hairpin DNA-functionalized gold colloids for the imaging of mRNA in live cells. J Am Chem Soc. 2010;132(28):9789–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lee M, Lee S, Lee J-H, Lim H-W, Seong GH, Lee EK, Chang S-I, Oh CH, Choo J. Highly reproducible immunoassay of cancer markers on a gold-patterned microarray chip using surface-enhanced Raman scattering imaging. Biosens Bioelectron. 2011;26(5):2135–41.

    Article  CAS  PubMed  Google Scholar 

  • Li H, Rothberg L. Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles. Proc Natl Acad Sci U S A. 2004;101(39):14036–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Li L, Zhao H, Chen Z, Mu X, Guo L. Aptamer-based electrochemical approach to the detection of thrombin by modification of gold nanoparticles. Anal Bioanal Chem. 2010;398(1):563–70.

    Article  CAS  PubMed  Google Scholar 

  • Li W, Wu P, Zhang H, Cai C. Catalytic signal amplification of gold nanoparticles combining with conformation-switched hairpin DNA probe for hepatitis C virus quantification. Chem Commun. 2012;48(63):7877–9.

    Article  CAS  Google Scholar 

  • Liu X, Dai Q, Austin L, Coutts J, Knowles G, Zou J, Chen H, Huo Q. A one-step homogeneous immunoassay for cancer biomarker detection using gold nanoparticle probes coupled with dynamic light scattering. J Am Chem Soc. 2008;130(9):2780–2.

    Article  CAS  PubMed  Google Scholar 

  • Lu W, Arumugam SR, Senapati D, Singh AK, Arbneshi T, Khan SA, Yu H, Ray PC. Multifunctional oval-shaped gold-nanoparticle-based selective detection of breast cancer cells using simple colorimetric and highly sensitive two-photon scattering assay. ACS Nano. 2010;4(3):1739–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Malou N, Raoult D. Immuno-PCR: a promising ultrasensitive diagnostic method to detect antigens and antibodies. Trends Microbiol. 2011;19(6):295–302.

    Article  CAS  PubMed  Google Scholar 

  • Mamas M, Dunn W, Neyses L, Goodacre R. The role of metabolites and metabolomics in clinically applicable biomarkers of disease. Arch Toxicol. 2011;85(1):5–17.

    Article  CAS  PubMed  Google Scholar 

  • Meng X, Zhou Y, Liang Q, Qu X, Yang Q, Yin H, Ai S. Electrochemical determination of microRNA-21 based on bio bar code and hemin/G-quadruplet DNAenzyme. Analyst. 2013;138(12):3409–15.

    Article  CAS  PubMed  Google Scholar 

  • Mirkin CA, Letsinger RL, Mucic RC, Storhoff JJ. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature. 1996;382(6592):607.

    Article  CAS  PubMed  Google Scholar 

  • Nam J-M, Thaxton CS, Mirkin CA. Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins. Science. 2003;301(5641):1884–6.

    Article  CAS  PubMed  Google Scholar 

  • Nam EJ, Kim EJ, Wark AW, Rho S, Kim H, Lee HJ. Highly sensitive electrochemical detection of proteins using aptamer-coated gold nanoparticles and surface enzyme reactions. Analyst. 2012;137(9):2011–6.

    Article  CAS  PubMed  Google Scholar 

  • Niu Y, Zhao Y, Fan A. Conformational switching immobilized hairpin DNA probes following subsequent expanding of gold nanoparticles enables visual detecting sequence-specific DNA. Anal Chem. 2011;83(19):7500–6.

    Article  CAS  PubMed  Google Scholar 

  • Perez JW, Vargis EA, Russ PK, Haselton FR, Wright DW. Detection of respiratory syncytial virus using nanoparticle amplified immuno-polymerase chain reaction. Anal Biochem. 2011;410(1):141–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Roy S, Soh JH, Gao Z. A microfluidic-assisted microarray for ultrasensitive detection of miRNA under an optical microscope. Lab Chip. 2011;11(11):1886–94.

    Article  CAS  PubMed  Google Scholar 

  • Song S, Liang Z, Zhang J, Wang L, Li G, Fan C. Gold-nanoparticle-based multicolor nanobeacons for sequence-specific DNA analysis. Angew Chem Int Ed. 2009;48(46):8670–4.

    Article  CAS  Google Scholar 

  • Stoeva SI, Lee J-S, Thaxton CS, Mirkin CA. Multiplexed DNA detection with biobarcoded nanoparticle probes. Angew Chem. 2006;118(20):3381–4.

    Article  Google Scholar 

  • Thaxton CS, Elghanian R, Thomas AD, Stoeva SI, Lee J-S, Smith ND, Schaeffer AJ, Klocker H, Horninger W, Bartsch G, Mirkin CA. Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy. Proc Natl Acad Sci. 2009;106(44):18437–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tu Y, Wu P, Zhang H, Cai C. Fluorescence quenching of gold nanoparticles integrating with a conformation-switched hairpin oligonucleotide probe for microRNA detection. Chem Commun. 2012;48(87):10718–20.

    Article  CAS  Google Scholar 

  • Uchida A, Kitayama Y, Takano E, Ooya T, Takeuchi T. Supraparticles comprised of molecularly imprinted nanoparticles and modified gold nanoparticles as a nanosensor platform. RSC Adv. 2013;3(47):25306–11.

    Article  CAS  Google Scholar 

  • Wang K, Tang Z, Yang CJ, Kim Y, Fang X, Li W, Wu Y, Medley CD, Cao Z, Li J, Colon P, Lin H, Tan W. Molecular engineering of DNA: molecular beacons. Angew Chem Int Ed. 2009;48(5):856–70.

    Article  CAS  Google Scholar 

  • Whitcombe MJ, Chianella I, Larcombe L, Piletsky SA, Noble J, Porter R, Horgan A. The rational development of molecularly imprinted polymer-based sensors for protein detection. Chem Soc Rev. 2011;40(3):1547–71.

    Article  CAS  PubMed  Google Scholar 

  • Williams TI, Toups KL, Saggese DA, Kalli KR, Cliby WA, Muddiman DC. Epithelial ovarian cancer: disease etiology, treatment, detection, and investigational gene, metabolite, and protein biomarkers. J Proteome Res. 2007;6(8):2936–62.

    Article  CAS  PubMed  Google Scholar 

  • Xu H, Mao X, Zeng Q, Wang S, Kawde A-N, Liu G. Aptamer-functionalized gold nanoparticles as probes in a dry-reagent strip biosensor for protein analysis. Anal Chem. 2008;81(2):669–75.

    Article  Google Scholar 

  • Yang X, Zhu J, Wang Q, Wang K, Yang L, Zhu H. A label-free and sensitive supersandwich electrochemical biosensor for small molecule detection based on target-induced aptamer displacement. Anal Methods. 2012;4(8):2221–3.

    Article  CAS  Google Scholar 

  • Zhang, D. et al. “Fluorescent bio-barcode DNA assay for the detection of Salmonella enterica serovar Enteritidis”. Biosensors and Bioelectronics 2009:24(5):1377–81.

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Du X, Huang X, Lv Z. Creating protein-imprinted self-assembled monolayers with multiple binding sites and biocompatible imprinted cavities. J Am Chem Soc. 2013;135(25):9248–51.

    Article  CAS  PubMed  Google Scholar 

  • Zhou W-H, Zhu C-L, Lu C-H, Guo X, Chen F, Yang H-H, Wang X. Amplified detection of protein cancer biomarkers using DNAzyme functionalized nanoprobes. Chem Commun. 2009;(44): 6845–7.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Joseph A. Conrad .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Wong, A.C., Wright, D.W., Conrad, J.A. (2014). Functionalized Gold Nanoparticles for Detection of Cancer Biomarkers. In: Preedy, V., Patel, V. (eds) General Methods in Biomarker Research and their Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7740-8_38-1

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-7740-8_38-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Online ISBN: 978-94-007-7740-8

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics