Differential sensing of base modifications in RNA nucleosides for accurate cancer diagnosis

The sensing and discrimination of different modified nucleosides are important in various key fields, including disease diagnosis and therapy, vaccine development, and so on. Due to the highly structural similarity and diversity of modified nucleosides, it is urgent but challenging to develop a simple and efficient method for accurate discrimination. Here, the discrimination and multiplex quantitation of modified RNA nucleoside are successfully achieved via a novel tetralactam macrocycle-based fluorescent sensor array for the first time. Based on the excellent ability of the endo-functionalized cavity of tetralactam macrocycle to distinguish structurally similar nucleobases in nucleosides, 16 nucleosides (including 4 unmodified, 6 methylated, and 6 other chemically modified nucleosides) with similar structures can be simultaneously discriminated with 100% accuracy. Furthermore, the concentrations of individual nucleosides in ternary mixtures are quantified simultaneously by support vector machine regression with high accuracy and immunity to interference, even in complicated human urine. In addition, the accurate discrimination of simulated cancer patient urine is realized by using the 3-element sensor array, validating its great potential in cancer precision medicine.