Covalent organic framework nanosheet anchored with highly dispersed Au nanoparticles as a novel nanoprobe for DNA methylation detection

Covalent-organic framework nanosheets (CONs) have received increasing attention in various fields. However, large-scale and high-yield preparation and flexible functionalization of CONs remain a chal-lenging task. Herein, we designed and fabricated a novel ultrathin (<5 nm) vinyl-functionalized CON in large scale (>80 mg) and high yield (>60 %) via an imine-exchange synthesis strategy. Through post -modification strategy, the vinyl-functionalized CONs were sequentially modified with thiols and Au nanoparticles with high distribution density (mass ratio of CONs to Au was about 4:1) and narrow size distribution (3.5 +/- 0.5 nm). The synthesized hybrid nanosheets were employed as material platform to design a novel nanoprobe for ultrasensitive detection towards cancer-associated methylated DNA. Integrating site-specific base oxidation damage strategy and target cyclic amplification effect, the well -designed CONs-based nanoprobe achieved high sensitivity for detecting methylated DNA as low as 10 fM and ultrahigh specificity for distinguishing 0.0001% methylation level. Noteworthy, the nanoprobe was successfully applied to the analysis of DNA methylation in human colon cancer cells, expanding the application scope of CONs and opening a new horizon to develop novel CONs-based nanoprobes.(c) 2022 Elsevier Inc. All rights reserved.