Diagnosing the miR-141 prostate cancer biomarker using nucleic acid-functionalized CdSe/ZnS QDs and telomerase. Issue 1 (26th September 2014)

• Record Type: Journal Article
• Authors: Jou, Amily Fang-ju; Lu, Chun-Hua; Ou, Yen-Chuan; Wang, Shian-Shiang; Hsu, Shih-Lan; Willner, Itamar; Ho, Ja-an Annie
• Is Part Of: Chemical science. Volume 6:Issue 1(2015:Jan.)
• Page Start: 659
• Page End: 665
• Publication Date: 2014-09-26
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c4sc02104e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : The miR-141 prostate cancer biomarker is optically detected by a two-step analytical platform that includes telomerase and semiconductor quantum dots. 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/H2 O2 . 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.