Quantitative and specific detection of exosomal miRNA using surface-enhanced Raman spectroscopy for accurate diagnosis of breast cancer

Abstract

MicroRNAs in exosomes (exosomal microRNAs) are attracting attention as cancer biomarkers for early diagnosis and prognosis due to their stability of body fluids. Since strong association exists between breast cancer and exosomal miRNA expression levels, it is important to develop effective methods that can monitor exosomal miRNA expression both over a wide range of concentrations and in ultralow amounts. Here, surface-enhanced-Raman scattering (SERS) based detection platform was developed for the quantitative analysis of exosomal miRNAs. The ultrasensitive detection of exosomal miRNA with single-nucleotide specificity was obtained by enhanced SERS signals from uniform plasmonic head-flocked gold nanopillar substrate, which generated multiple hotspots and enabled hybridization between short oligonucleotides, i.e., miRNAs and LNA probes. The proposed SERS sensor showed ultra-low detection limit without any amplification process, multiplex sensing capabilities, a wide dynamic range (1 aM to 100 nM) and sound miRNA recovery in serum. In addition, this sensor allowed to reliably observe exosomal miRNA expression patterns in breast cancer cell lines and is possible to discriminate breast cancer subtypes based on the difference in these expression patterns. Our results suggest that this sensor can be used for a universal cancer diagnosis cancer diagnosis and further biomedical applications through the quantitative measurement of exosomal miRNAs in body fluids.