Detection of telomerase activity at the single-cell level is one of the central challenges in cancer diagnostics and therapy. Herein, we describe a facile and reliable point-of-care testing (POCT) strategy for detection of telomerase activity via a portable pressure meter. Telomerase primer (TS) was immobilized onto the surface of magnetic beads (MBs), and then was elongated to a long single-stranded DNA by telomerase. The elongated (TTAGGG) repeat unit hybridized with several short PtNP-functionalized complementary DNA (PtNPs-cDNA), which specifically enriched PtNPs onto the surfaces of magnetic beads (MBs), which were separated using a magnet. Then, nanoparticle-catalyzed gas-generation reaction converted telomerase activity into significant change in gas pressure. Because of the self-amplification of telomerase and enrichment by magnetic separation, the diluted telomerase equivalent to a single HeLa cell was facilely detected. More importantly, the telomerase in the lysate of 1 HeLa cell can be reliably detected by monitoring change in gas pressure, indicating that it is feasible and possible to study differences between individual cells. The difference in relative activity between different kinds of cancer cells was easily and sensitively studied. Study of inhibition of telomerase activity demonstrated that our method has great potential in screening of telomerase-targeted antitumor drugs as well as in clinical diagnosis.
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http://dx.doi.org/10.1021/acs.analchem.7b01529 | DOI Listing |
Adv Sci (Weinh)
December 2024
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Increased telomerase activity has been considered as a conspicuous sign of human cancers. The catalytic cores of telomerase involve a reverse transcriptase and the human telomerase RNA (hTR). However, current detection of telomerase is largely limited to its activity at the tissue and single-cell levels.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, HarBin Medical University, Harbin, PR China. Electronic address:
The telomeric G-quadruplex (G4) along with the telomerase catalytic subunit hTERT are crucial in the extension of telomeres. Tumor cells can establish replicative immortality by activating the telomere-maintenance mechanism (TMM).Small molecule ligands can limit cancer telomere lengthening by by targeting at G4 and hTERT.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2024
Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, 200 Hui He Road, Wuxi, Jiangsu, 214062, China.
Gastric cancer (GC) is one of the most common cancers worldwide, with increasing incidence and mortality rates. It is typically diagnosed at advanced stages, leading to a poor prognosis. GC is a highly heterogeneous disease and its progression is associated with complex interplay between genetic and environmental factors.
View Article and Find Full Text PDFACS Omega
December 2024
Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Telomerase activation can lead to the escape from cell senescence and immortalization, playing a crucial role in the growth and proliferation of cancer cells. Therefore, the detection of telomerase activity is essential for cancer diagnosis and treatment. Herein, we develop a novel ultrasensitive and visually detectable platform.
View Article and Find Full Text PDFLife Sci
December 2024
Department of Pharmacology, School of Pharmacy, Nantong University, Nantong 226001, China. Electronic address:
Aims: High telomerase activity has been detected in over 85 % of tumors, with the activation of hTERT being the most crucial mechanism for re-establishing telomerase activity. Activation of hTERT maintains telomere length in cells, enabling cancer cells to proliferate indefinitely. Nevertheless, the specific mechanism of telomerase activation in non-small cell lung cancer (NSCLC) remains unclear, and post-transcriptional regulation of hTERT could be a potential activation mechanism.
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