A magnetic-plasmonic SERS biosensor for detection of circular RNA toward tumor diagnosis

Circular RNAs (circRNAs) have recently emerged as promising biomarkers for the early diagnosis of cancer and the development of targeted therapeutic strategies. However, their detection remains challenging due to their low abundance and the difficulty in discriminating them from their linear RNA counterparts. Herein, a surface-enhanced Raman scattering (SERS) biosensor employing magnetic-plasmonic nanoparticles was proposed for the specific detection of circCDR1as, a tumor-associated circular RNA antisense to the cerebellar degeneration-related protein 1 transcript. The detection approach involves initially capturing the target molecule with gold-coated magnetic beads, which allows for magnetic separation and enrichment. Then, plasmonic nanoparticles labeled with a Raman reporter (5,5'-dithio bis-(2-nitrobenzoic acid), DTNB) attach to the bead surface through complementary hybridization, forming a core-satellite structure that greatly enhances the SERS signal. Quantification of the target is achieved by measuring the intensity of the DTNB Raman signal. This method demonstrated sensitive and selective detection of a circCDR1as mimic, with a detection limit of 1 pM. Furthermore, the biosensor effectively discriminated breast cancer cells (MDA-MB-231) from normal breast epithelial cells (MCF-10A) by detecting markedly elevated levels of circCDR1as in the malignant cells. Overall, this work introduces a novel nanotechnology-based platform for circRNA detection, underscoring its considerable potential for applications in cancer diagnosis and gene therapy monitoring.