Dual biomineralized metal-organic frameworks-mediated conversion of chemical energy to electricity enabling portable PEC sensing of telomerase activity in bladder cancer tissues

In this work, we report on a portable photoelectrochemical (PEC) sensing system for telomerase activity detection based on dual biomineralized ZIF-8 nanoparticles (NPs)-medicated conversion of chemical energy to electricity and terminal deoxynucleoside transferase (TdTase)-catalyzed elongation of Y-junction DNA structure. Two kinds of biomineralized ZIF-8 NPs including glucose oxidase (GOx)-encapsulated ZIF-8 (GZIF) and horse-radish peroxidase (HRP)-encapsulated ZIF-8 (HZIF) are involved in this assay system. The recognition of telomerase is started with telomerase-catalyzed elongation of a telomerase substrate (TS) primer, which generates a longer elongation chain to trigger the formation of a Y-junction DNA structure. The Y-junction DNA with abundant 3'-OH terminal and small steric hindrance facilitates the implement of TdTase-catalyzed elongation reaction, in which the branches of Y-junction DNA are elongated and endowed with biotin moiety to capture streptavidin-modified GZIF (SA-GZIF). The signal transduction is then achieved on a luminol/HZIF/CdS-based photoelectrode. Once the H2O2 produced from GZIF-catalyzed hydrolysis of glucose is introduced to the photoelectrode, chemiluminescence of HRP-luminol-H2O2-p-iodo-phenol (PIP) system confined in HZIF is activated to excite photocurrent of CdS NPs, which is then recorded by a portable digital multimeter (DMM). The developed PEC sensing system possesses a wide calibration range from 50 to 5000 HeLa cells and a low detection limit of 46 cells. Significantly, the sensing platform is successfully applied to evaluate the telomerase activity in resected bladder tumor tissues. This work not only provides a diagnostic tool for telomerase-related diseases but also open a new avenue for establishing PEC assay methods using metal-organic framework (MOF) NPs.