Metabolic Footprinting-Based DNA-AuNP Encoders for Extracellular Metabolic Response Profiling

Metabolic footprinting as a convenient and non-invasive cell metabolomics strategy relies on monitoring the whole extracellular metabolic process. It covers nutrient consumption and metabolite secretion of in vitro cell culture, which is hindered by low universality owing to pre-treatment of the cell medium and special equipment. Here, we report the design and a variety of applicability, for quantifying extracellular metabolism, of fluorescently labeled single-stranded DNA (ssDNA)-AuNP encoders, whose multi-modal signal response is triggered by extracellular metabolites. We constructed metabolic response profiling of cells by detecting extracellular metabolites in different tumor cells and drug-induced extracellular metabolites. We further assessed the extracellular metabolism differences using a machine learning algorithm. This metabolic response profiling based on the DNA-AuNP encoder strategy is a powerful complement to metabolic footprinting, which significantly applies potential non-invasive identification of tumor cell heterogeneity.

Automated summary

Metabolic footprinting is a convenient and non-invasive cell metabolomics strategy used to monitor the entire extracellular metabolic process. However, its universality is limited due to the need for pre-treatment of cell medium and specialized equipment. In this study, we developed a fluorescently labeled single-stranded DNA-AuNP encoder that can detect extracellular metabolites, allowing for metabolic response profiling and the identification of cell heterogeneity in tumor cells.