Rapid and Label‐Free Detection of 5‐Hydroxymethylcytosine in Genomic DNA Using an Au/ZnO Nanorods Hybrid Nanostructure‐Based Electrochemical Sensor

Abstract

Ten-eleven-translocation (TET) proteins modify DNA methylation by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Loss of 5hmC, a widely accepted epigenetic hallmark of cancers, is proposed as a biomarker for early cancer diagnosis and prognosis. Thus, precise quantification of 5hmC holds great potential for diverse clinical applications. DNAs containing 5mC or 5hmC display different adsorption affinity toward the gold surface, thus producing different electrochemical responses. Here a novel, label-free electrochemical sensor based on gold nanoparticles (Au NPs)/zinc oxide nanorods (ZnO NRs) nanostructure for the facile and real-time detection of 5hmC-enriched DNAs is reported. The hybrid structure is fabricated by the vertical hydrothermal growth of ZnO NRs onto indium tin oxide glass substrate, followed by the decoration of ZnO NRs with Au NPs via sputtering. Successful fabrication is confirmed by analyzing the morphology and chemical composition of the sensor. By coupling the fabricated sensor with cyclic voltammetry, its functionality in distinguishing genomic DNAs containing different levels of 5hmC is validated. Notably, the sensor device successfully and consistently detects 5hmC loss in primary hepatocellular carcinoma, compared to the normal tissues. Thus, the novel sensing strategy to assess DNA hydroxymethylation will likely find broad applications in early cancer diagnosis and prognosis evaluation.

Recent progress of biosensors for the detection of lung cancer markers

“…The real-time detection of 5hmC using a novel labelfree electrochemical sensor enriched DNA based on nanostructures of gold nanoparticles and zinc oxide nanorods. 201 The voltammetric techniques for proteins are realized by the combination of the antigen and antibody. [192][193][194]200 The sensor uses single-walled carbon nanotubes, carbon nano-onions, gold nanoparticles, and chitosan as well as nanomaterials to detect the CEA.…”

“…The real-time detection of 5hmC using a novel label-free electrochemical sensor enriched DNA based on nanostructures of gold nanoparticles and zinc oxide nanorods. 201…”

Upconversion Material–Plasmonic Metal–Semiconductor Ternary Heteronanostructures for Wide-Range Solar-to-Chemical Energy Conversion

“…Devising multicomponent hybrid nanostructures has been extensively studied because of their potential in various applications, such as sensing, , medical treatment, , energy storage, , and catalysis. − Particularly, plasmonic metal–semiconductor heteronanostructures have emerged as a promising platform for solar-to-chemical energy conversion. − Due to the promoted charge carrier generation in semiconductors through the transfer of plasmon energy resulting from the excitation of the localized surface plasmon resonance (LSPR) of plasmonic metals to semiconductors, such heteronanostructures have shown excellent photocatalytic performance under visible light as well as ultraviolet (UV) light irradiation . Recently, significant efforts have been made to extend the working wavelength range of plasmonic metal–semiconductor hybrids to longer wavelengths by modulating their LSPR characteristics, ,,− especially toward near-infrared (NIR) region that occupies ∼50% energy of sunlight .…”

Electrochemical Sensing of Uric Acid with Zinc Oxide Nanorods Decorated with Copper Oxide Nanoseeds

“…and their nanocomposites (i.e., ZnO-CuO, ZnO-Au, ZnO-Fe 2 O 3 , ZnO-polyaniline, ZnO-MWCNTs, etc.) have been utilized for fabrication of electrochemical-based sensors (enzymatic/non-enzymatic) for detection of different biomolecules and for health sciences. − Mainly, zinc oxide (ZnO) nanostructures have been employed in designing improved sensors due to their easy and cost-effective synthesis approach, high surface-to-volume ratio, and being easily modified with other metal/metal oxides. − However, ZnO nanomaterial-based hybrid nanostructures are preferred nanomaterials for the fabrication of different sensing devices with enhanced sensing properties compared to only ZnO nanostructure-based sensors. − For example, recently, Sideeq Bhat et al used hybrid nanostructures of Au-ZnO NRs for the fabrication of an electrochemical-based sensor . They reported enhanced electrochemical properties of Au nanoparticle-modified ZnO nanorods while detecting 5-hydroxymethylcytosine in genomic DNA.…”

“…27−38 However, ZnO nanomaterial-based hybrid nanostructures are preferred nanomaterials for the fabrication of different sensing devices with enhanced sensing properties compared to only ZnO nanostructure-based sensors.39−49 For example, recently, Sideeq Bhat et al used hybrid nanostructures of Au-ZnO NRs for the fabrication of an electrochemical-based sensor 39. They reported enhanced electrochemical properties of Au nano-…”