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Issue 1, 2015
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Diagnosing the miR-141 prostate cancer biomarker using nucleic acid-functionalized CdSe/ZnS QDs and telomerase

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Abstract

The microRNA, miR-141, is a promising biomarker for prostate cancer. We implement here a two-step sensing platform for the sensitive detection of miR-141. The first step involves the use of semiconductor CdSe/ZnS quantum dots (QDs) modified by FRET quencher-functionalized nucleic acids, that include the recognition sequence for miR-141 and a telomerase primer sequence for the second step of the analytical platform. Subjecting the probe-modified QDs to miR-141, in the presence of duplex specific nuclease, DSN, leads to the formation of a miR-141/probe duplex and to its DSN-mediated cleavage, while regenerating the miR-141. The DSN-induced cleavage of the quencher units leads to the activation of the fluorescence of the QDs, thus allowing the optical detection of miR-141 with a sensitivity corresponding to 1.0 × 10−12 M. The nucleic acid residues associated with the QDs after cleavage of the probe nucleic acids by DSN act as primers for telomerase. The subsequent telomerase/dNTPs-stimulated elongation of the primer units forms G-quadruplex telomer chains. Incorporation of hemin in the resulting G-quadruplex telomer chains yields horseradish peroxidase-mimicking DNAzyme units, that catalyze the generation of chemiluminescence in the presence of luminol/H2O2. The resulting chemiluminescence intensities provide a readout signal for miR-141, DL = 2.8 × 10−13 M. The first step of the sensing platform is non-selective toward miR-141 and the resulting fluorescence may be considered only as an indicator for the existence of miR-141. The second step in the sensing protocol, involving telomerase, provides a selective chemiluminescence signal for the existence of miR-141. The two-step sensing platform is implemented for the analysis of miR-141 in serum samples from healthy individuals and prostate cancer carriers. Impressive discrimination between healthy individuals and prostate cancer carriers is demonstrated.

Graphical abstract: Diagnosing the miR-141 prostate cancer biomarker using nucleic acid-functionalized CdSe/ZnS QDs and telomerase

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Publication details

The article was received on 16 Jul 2014, accepted on 28 Aug 2014 and first published on 09 Sep 2014


Article type: Edge Article
DOI: 10.1039/C4SC02104E
Chem. Sci., 2015,6, 659-665
  • Open access: Creative Commons BY-NC license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Diagnosing the miR-141 prostate cancer biomarker using nucleic acid-functionalized CdSe/ZnS QDs and telomerase

    A. F. Jou, C. Lu, Y. Ou, S. Wang, S. Hsu, I. Willner and J. A. Ho, Chem. Sci., 2015, 6, 659
    DOI: 10.1039/C4SC02104E

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