Harnessing Nanomaterials for Next-Generation DNA Methylation Biosensors

DNA methylation is an epigenetic mechanism that regulates gene expression and is implicated in diseases such as cancer and atherosclerosis. However, traditional clinical methods for detecting DNA methylation often lack sensitivity and specificity, making early diagnosis challenging. Nanomaterials offer a solution with their unique properties, enabling highly sensitive photochemical and electrochemical detection techniques. These advanced methods enhance the accuracy and efficiency of identifying DNA methylation patterns, providing a powerful tool for early diagnosis and treatment of methylation-related diseases. This review summarizes nanomaterial-based techniques, categorized into electrochemical and photochemical methods for developing next-generation biosensors for DNA methylation. Electrochemical approaches based on nanostructured or nanomaterial-modified electrodes can detect methylation through electrical signals and can directly identify methylation sites via ionic current changes based on nanopore sequencing. Photochemical methods based on nanoparticles allow for optical detection through colorimetry, fluorescence, surface plasmon resonance, and Raman spectroscopy. Nanotechnology-implemented methodologies enable ultrasensitive and selective biosensors as point-of-care platforms for DNA methylation analysis, thereby advancing epigenetic research and clinical diagnostics.