Oncometabolite Fingerprinting Using Fluorescent Single-Walled Carbon Nanotubes

The production of oncometabolites is the direct result of mutagenesis in key cellular metabolic enzymes, appearing typically in cancers such as glioma, leukemia, and glioblastoma. Once accumulated, oncometabolites promote cancerous transformations by interfering with important cellular functions. Hence, the ability to sense and quantify oncometabolites is essential for cancer research and clinical diagnosis. Here, the authors present a near-infrared optical nanosensor for a known oncometabolite, D-2-hydroxyglutarate (D2HG), discovered in a screening of a library of fluorescent single-walled carbon nanotubes (SWCNTs) functionalized with ssDNA. The screening reveals (ATTT)₇-SWCNT as a sensor for D2HG, exhibiting a fluorescence intensity increase upon the interaction with D2HG. The fluorescence response of the sensor does not appear to be attributed to basic chemical features of the target analytes tested, and is shown to discriminate D2HG from other related metabolites, including its enantiomer L-2-hydroxyglutarate. Further, the fluorescence modulation is dependent on the analyte concentration and the SWCNT chirality, showing up to 40.7% and 28.2% increase of the (6,5)-chirality peak and the (9,5)- and (8,7)-chirality joint peak, at 572 and 730 nm excitation, respectively, in the presence of 10 mm D2HG. This work opens new opportunities for molecular recognition of oncometabolites which can advance basic cancer metabolism research.