Click chemistry-based dual nanosystem for microRNA-122 detection with single-base specificity from tumour cells

• Published in: Journal of nanobiotechnology 2024-12, Vol.22 (1), p.791-16, Article 791
• Main Authors: Robles-Remacho, Agustín, Martos-Jamai, Ismael, Tabraue-Chávez, Mavys, Aguilar-González, Araceli, Laz-Ruiz, Jose A, Cano-Cortés, M Victoria, López-Delgado, F Javier, Guardia-Monteagudo, Juan J, Pernagallo, Salvatore, Diaz-Mochon, Juan J, Sanchez-Martin, Rosario M
• Format: Article
• Language: English
• Subjects: Biological markers; Biomarkers, Tumor - genetics; Bioorthogonal chemistry; Cancer; Cell Line, Tumor; Chemical properties; Chemical reactions; Click chemistry; Click Chemistry - methods; Diagnosis; Flow Cytometry - methods; Humans; Measurement; Microribonucleic acid; MicroRNA; MicroRNAs - genetics; miR-122; Molecular diagnostic techniques; Nanoparticles; Nanoparticles - chemistry; Nanosystem; Oncology, Experimental
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-024-03071-6

MicroRNAs (miRNAs) have been recognised as potential biomarkers due to their specific expression patterns in different biological tissues and their changes in expression under pathological conditions. MicroRNA-122 (miR-122) is a vertebrate-specific miRNA that is predominantly expressed in the liver and plays an important role in liver metabolism and development. Dysregulation of miR-122 expression is associated with several liver-related diseases, including hepatocellular carcinoma and drug-induced liver injury (DILI). Given the potential of miR-122 as a biomarker, its effective detection is important for accurate diagnosis. However, miRNA detection methods still face challenges, particularly in terms of accurately identifying miRNA isoforms that may differ by only a single base. Here, with the aim of advancing accessible methods for the detection of miRNAs with single-base specificity, we have developed a robust dual nanosystem that leverages the simplicity of click chemistry reactions. Using the dual nanosystem, we successfully detected miR-122 at single-base resolution using flow cytometry and analysed its expression in various tumour cell lines with high specificity and strong correlation with TaqMan assay results. We also detected miR-122 in serum and identified four single nucleotide variations in its sequence. The chemistry employed in this dual nanosystem is highly versatile and offers a promising opportunity to develop nanoparticle-based strategies that incorporate click chemistry and bioorthogonal chemistry for the detection of miRNAs and their isoforms.