Abstract
MicroRNAs are small RNAs which regulate gene expression by translational repression or degradation of messenger RNAs. Regards to important role of these biomolecules in human disease progress, to produce sensitive, simple and cost-effective assays for microRNAs are in urgent demand. miR-137 in Alzheimer’s patients has demonstrated its potential as non-invasive biomarkers in blood for Alzheimer’s disease diagnosis and prognosis. This paper describes a novel, sensitive and specific microRNA assay based on Colorimetric detection of gold nanoparticles and hybridization chain reaction amplification (HCR). The new strategy eliminates the need for enzymatic reactions, chemical changes, separation processes and sophisticated equipment. The detection process is visible with the naked eyes and detection limit for this method is 0.25nM which is less than or at least comparable with the previous methods based on colorimetric of AuNPs. The important features of this method are high sensitivity and specificity to differentiate between perfectly matched, mismatched and non-complementary target microRNAs and also decent response in the real sample analysis with blood plasma. In conclusion, the simple and fast nanobiosensor can clinically be used for the early detection of Alzheimer’s disease by direct detection of the plasma miR-137 in real clinical samples, without a need for sample preparation, RNA extraction and/or amplification.
Similar content being viewed by others
References
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3(3):186–191
Rao AT, Degnan AJ, Levy LM (2014) Genetics of Alzheimer disease. AJNR Am J Neuroradiol 35(3):457–458
Hizir MS, Balcioglu M, Rana M, Robertson NM, Yigit MVV (2014) Simultaneous detection of circulating oncomiRs from body fluids for prostate cancer staging using nanographene oxide. ACS Appl Mater Interfaces 6(17):14772–14778
Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6(11):857–866
Azimzadeh M, Rahaie M, Nasirizadeh N, Ashtari K, Naderi-Manesh H (2016) An electrochemical nanobiosensor for plasma miRNA-155, based on graphene oxide and gold nanorod, for early detection of breast cancer. Biosens Bioelectron 77:99–106
Delay C, Mandemakers W, Hébert SS (2012) MicroRNAs in Alzheimer’s disease. Neurobiol Dis 46:285–290
Grasso M, Piscopo P, Confaloni A, Denti MA (2014) Circulating miRNAs as biomarkers for neurodegenerative disorder. Molecules 19(5):6891–6910
Ebert MS, Sharp PA (2012) Roles for MicroRNAs in conferring robustness to biological processes. Cell 149(3):515–524
Dorval V, Nelson PT, Hébert SS (2013) Circulating microRNAs in Alzheimer’s disease: the search for novel biomarkers. Front Mol Neurosci 6:24
Geekiyanage H, Chan C (2011) MicroRNA-137/181c regulates serine palmitoyltransferase and in turn amyloid beta, novel targets in sporadic Alzheimer’s disease. J Neurosci 31(41):14820–14830
Geekiyanage H, Jicha GA, Nelson PT, Chan C (2012) Blood serum miRNA: non-invasive biomarkers for Alzheimer’s disease. Exp Neurol 235(2):491–496
Kumar P, Dezso Z, MacKenzie C, Oestreicher J, Agoulnik S, Byrne M, Bernier F, Yanagimachi M, Aoshima K, Oda Y (2013) Circulating miRNA biomarkers for Alzheimer’s disease. PLoS ONE 8(7), e69807
Li J, Yao B, Huang H, Wang Z, Sun CH, Fan Y, Chang Q, Li SL, Wang X, Xi JZ (2009) Real-time polymerase chain reaction MicroRNA detection based on enzymatic stem-loop probes ligation. Anal Chem 81(13):5446–5451
Yu CY, Yin BC, Ye BC (2013) A universal real-time PCR assay for rapid quantification of microRNAs via the enhancement of base-stacking hybridization. Chem Commun 49:8247–8249
Castoldi M, Schmidt S, Benes V, Hentze MW, Muckenthaler MU (2008) miChip: an array-based method for microRNA expression profiling using locked nucleic acid capture probes. Nat Protoc 3(2):321–329
Várallyay E, Burgyán J, Havelda Z (2008) MicroRNA detection by northern blotting using locked nucleic acid probes. Nat Protoc 3(2):190–196
EunKim J, Choi J, Colas M, HaKim D, Lee H (2016) Gold-based hybrid nanomaterials for biosensing and molecular diagnostic applications. Biosens Bioelectron 80:543–559
Xia F, Zuo X, Yang R, Xiao Y, Kang D, Vallée-Bélisle A, Gong X, Yuen JD, Hsu BB, Heeger AJ, Plaxco KW (2010) Colorimetric detection of DNA, small molecules, proteins, and ions using unmodified gold nanoparticles and conjugated polyelectrolytes. Proc Natl Acad Sci U S A 107(24):10837–10841
Li J, Fu H-E, Wu L-J, Zheng A-X, Chen G-N, Yang H-H (2012) General colorimetric detection of proteins and small molecules based on cyclic enzymatic signal amplification and hairpin aptamer probe. Anal Chem 84(12):5309–5315
Li RD, Yin BC, Ye BC (2016) Ultrasensitive, colorimetric detection of microRNAs based on isothermal exponential amplification reaction-assisted gold nanoparticle amplification. Biosens Bioelectron 86:1011–1016
Xia N, Zhang L, Wang G, Feng Q, Liu L (2013) Label free and sensitive strategy for microRNAs detection based on the formation of boronate ester bonds and the dual amplification of gold nanoparticles. Biosens Bioelectron 47:461–466
Dirks RM, Pierce NA (2004) Triggered amplification by hybridization chain reaction. Proc Natl Acad Sci U S A 101(43):15275–15278
Liu P, Yang X, Sun S, Wang Q, Wang K, Huang J, Liu J, He L (2013) Enzyme-free colorimetric detection of DNA by using gold nanoparticles and hybridization chain reaction amplification. Anal Chem 85(16):7689–7695
Turkevich J, Stevenson PC, Hillier J (1951) A study of the nucleation and growth processes in the synthesis of colloidal gold. Discuss Faraday Soc 11:55–75
Volkert AA, Subramaniam V, Haes AJ (2011) Implications of citrate concentrationduring the seeded growth synthesis of gold nanoparticles. Chem Commun 47:478–480
Rahaie M, Ghai R, Babic B, Dimitrov K (2009) Synthesis and characterization of DNA-based micro- and nanodumbbell structures. J Bionanosci 3:73–79
Lyubchenko YL, Shlyakhtenko LS, Ando T (2011) Imaging of nucleic acids with atomic force microscopy. Methods 54(2):274–283
Zhilei G, Meihua L, Ping W, Hao P, Juan Y, Jiye S, Qing H, Dannong H, Chunhai F, Xiaolei Z (2014) Hybridization chain reaction amplification of MicroRNA detection with a tetrahedral DNA nanostructure-based electrochemical biosensor. Anal Chem 86(4):2124–2130
Li H, Rothberg L (2004) Colorimetric detection of DNA sequences based on electrostatic interactions with unmodified gold nanoparticles. Proc Natl Acad Sci U S A 101(39):14036–14039
Deng H, Zhang X, Kumar A, Zou G (2013) Long genomic DNA amplicons adsorption onto unmodified gold nanoparticles for colorimetric detection of Bacillus anthracis. Chem Commun 49(1):51–53
Seow N, Tan YN, Yung L-YL (2014) Gold nanoparticle–dynamic light scattering tandem for the rapid and quantitative detection of the let7 MicroRNA family. Part Part Syst Charact 31(12):1260–1268
Rosi NL, Mirkin CA (2005) Nanostructures in biodiagnostics. Chem Rev 105(4):1547–1562
Acknowledgements
We would to thank the University of Tehran for providing financial and instrumental supports in this work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Delkhahi, S., Rahaie, M. & Rahimi, F. Design and Fabrication a Gold Nanoparticle-DNA Based Nanobiosensor for Detection of microRNA Involved in Alzheimer's Disease. J Fluoresc 27, 603–610 (2017). https://doi.org/10.1007/s10895-016-1988-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10895-016-1988-8