Ultra-stable fluorinated poly-A spherical nucleic acid for high-fidelity intracellular MiRNA-21 imaging

Polyadenine (poly-A) based spherical nucleic acids (SNAs) have received substantial attention owing to their precise regulation of DNA density and orientation by adjusting the length of adenine bases, which enhances the efficiency of DNA hybridization and sensitivity of target detection. Their application, however, is limited by poor stability under high salt conditions or prolonged storage, and insufficient resistance to biological thiols. In this study, a 2'-fluorinated poly-A (FpA) functionalized SNAs (Au/FpA) has been constructed to address these issues. The resulting Au/FpA can complete the entire preparation process within 1.5 h and exhibit stability under high temperatures (up to 90 °C), high salt concentrations (up to 0.8 M NaCl), and a broad pH range (3-12). Furthermore, an Au/FpA probe was constructed for the accurate and high-efficiency imaging of microRNA (miRNA) in living cells. The Au/FpA probe maintained the high-fidelity performance characteristics of Au/FpA SNAs, effectively resisting biological thiol interference and accurately identifying target cancer cells in mixed culture systems. These fluorinated poly-A-based SNAs offer an efficient method for the rapid preparation of high-performance SNAs and open new avenues for innovative designs in biosensing and clinical diagnostic applications.