A resonance Rayleigh scattering sensor for sensitive differentiation of telomere DNA length and monitoring special motifs (G-quadruplex and i-motif) based on the Ag nanoclusters and NAND logic gate responding to chemical input signals

Abstract

BackgroundDifferentiation of telomere length is of vital importance because telomere length is closely related with several deadly diseases such as cancer. Additionally, G-quadruplex and i-motif formation in telomeric DNA have been shown to act as a negative regulator of telomere elongation by telomerase in vivo and are considered as an attractive drug target for cancer chemotherapy.ResultsIn this assay, Ag nanoclusters templated by hyperbranched polyethyleneimine (PEI–Ag NCs) are designed as a new novel resonance Rayleigh scattering (RRS) probe for sensitive differentiation of telomere length and monitoring special motifs (G-quadruplex and i-motif). In this assay, free PEI–Ag NC probe or DNA sequence alone emits low intensities of RRS, while the formation of PEI–Ag NCs/DNA complexes yields greatly enhanced RRS signals; however, when PEI–Ag NCs react with G-quadruplex or i-motif, the intensities of RRS exhibit slight changes. At the same concentration, the enhancement of RRS signal is directly proportional to the length of telomere, and the sensitivity of 64 bases is the highest with the linear range of 0.3–50 nM (limit of detection 0.12 nM). On the other hand, due to the conversion of telomere DNA molecules among multiple surrounding conditions, a DNA logic gate is developed on the basis of two chemical input signals (K+ and H+) and a change in RRS intensity as the output signal.ConclusionOur results indicate that PEI–Ag NCs can serve as a novel RRS probe to identify DNA length and monitor G-quadruplex/i-motif through the different increasing degrees of RRS intensity. Meanwhile, the novel attributes of the nanoprobe stand superior to those involving dyes or labeled DNA because of no chemical modification, low cost, green, and high efficiency.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0407-5) contains supplementary material, which is available to authorized users.

Telomerase: a nexus between cancer nanotherapy and circadian rhythm

“…Additionally, interactions of PEI-AgNCs with GQ or i-motifs result in slight changes in RRS intensities. 40 In an alternative experiment, genomic DNA extracted from samples is affixed to SERS probes, which are then deposited onto an SERS substrate composed of assembled silver nanoparticles (AgNPs), followed by SERS measurement. Greater telomere length leads to an increased number of telomere probes being attached, consequently producing a more prominent SERS signal.…”

A dual-amplification strategy-intergated SERS biosensor for ultrasensitive hepatocellular carcinoma-related telomerase activity detection

“…In this sense, development of relevant biomarkers to assist the early-stage diagnosis is a priority. Telomerase is a ribonucleoprotein enzyme elongating telomeric DNA, whose differential expression in normal tissues and tumor cells makes it an attractive biomarker for HCC diagnostic and prognostic (Wang et al, 2018;Afshari et al, 2022;Manganelli et al, 2022). Researchers have found that quantitative assay of telomerase can provide a satisfactory positive rate for HCC diagnosis compared to alpha-fetoprotein (AFP) and PIVKA-II (Tzartzeva and Singal., 2018).…”