DNAzyme-Mediated Biodeposition Coupling Adjustable Cascade Electric Fields for Photoelectrochemical Telomerase Activity Monitoring.

Telomerase, as a specialized reverse transcriptase, plays a vital role in early cancer diagnostics and prognosis; thus, developing efficient sensing technologies is of vital importance. Herein, an innovative "signal-on-off" photoelectrochemical (PEC) sensing platform was developed for ultrasensitive evaluation of telomerase activity based on an electron-transfer tunneling distance regulation strategy and DNAzyme-triggerable biocatalytic precipitation. Concretely, cascade internal electric fields between CuInS 2 quantum dots (QDs), graphitic carbon nitride nanosheets (g-C 3 N 4 NSs), and TiO 2 nanorod arrays (NRAs) were developed to realize cascade electron extraction and hole transfer. Enabled by such a design, an effective "signal-on" state to gain a progressively enhanced PEC output was designed by suppressing the photogenerated electron-hole pair recombination. With the introduction of hairpin probe H2 and the subsequent extension of the primer sequence driven by the target telomerase, the CuInS 2 QDs labeled with hairpin probe H1 were programmatically unfolded, resulting in CuInS 2 QDs' close proximity to the working electrode away from the cascade interface, accompanied by the formation of G-quadruplex/hemin complexes. The gradual undermining of tunneling distance and implantation of DNAzyme-initiating biocatalytic precipitation tremendously induced the sluggish migration kinetics of the photoinduced charge, accompanied by the photocurrent intensity decrement, leading to the "signal-off" state. Under optimized conditions, the as-prepared PEC biosensor realizes ultrasensitive detection of telomerase activity from 10 to 10 5 cell·mL -1 with a detection limitation of 3 cells·mL -1 . As a proof of concept, this well-designed method provides new insights into signal amplification for telomerase activity evaluation and also presents promising potential for further development in drug screening, healthcare diagnostics, and biological assays.