Electron transfer-driven ultrathin nanozyme synergizes with nucleic acid amplification for bladder cancer screening.

MicroRNA-21 (miR-21) is a key bladder cancer diagnostic biomarker, but its ultra-low abundance and matrix interference in clinical samples impede accurate detection. Herein, we developed a sensitive electrochemical biosensor integrating CHA-HCR cascade amplification with oxygen vacancy (OVac)-rich ultra-thin core-shell Au@MnO2 nanozymes for clinical miR-21 detection. The Au@MnO2 exhibited excellent oxidase-mimicking activity: δ-MnO2 shell OVac form efficient electron transfer pathways (reducing environmental sensitivity), while the Au core accelerates electron transfer, synergistically enhancing signals. miR-21 triggers CHA amplification; its products induce HCR to form long-chain DNA that captured by nanozymes, achieving efficient signal amplification via the masked active sites. Under optimal conditions, the biosensor establishes a detection range of 10 fM-10 nM (LOD: 1.32 fM) with superior selectivity and stability. Notably, it accurately detects miR-21 in urine samples, with results highly consistent with PCR (nucleic acid detection gold standard), confirming clinical practicality. This biosensor provides a reliable supplementary platform for bladder cancer diagnosis.