Yu Cui, Liuyi Huang, Jingwen Zhao, Jiyang Liu, W W Hu
ABSTRACT The precise quantification of cytokines is crucial for monitoring disease onset and progression. Herein, we developed a synergistic signal amplification approach by utilizing nanoreactor‐encapsulated CeO 2 nanozymes, which were in situ electrodeposited within the mesoporous silica nanochannel film (SNF) grown on indium tin oxide (ITO) electrodes (CeO 2 @SNF/ITO). Notably, CeO 2 @SNF/ITO possesses bifunctional enzyme‐like activities, enabling efficient regulation of two co‐reactants, including endogenous dissolved oxygen (DO) and exogenous hydrogen peroxide (H 2 O 2 ). Under neutral pH conditions, electrochemical reduction of the encapsulated CeO 2 leads to the transformation of Ce(IV) into Ce(III). The resulting Ce(III) species not only facilitates the oxygen reduction reaction through its oxidase‐like activity but also catalyzes H 2 O 2 decomposition via peroxidase‐like behavior. This process leads to the abundant generation of reactive oxygen species (ROS), which can effectively oxidize luminol anions, thereby significantly enhancing the cathodic electrochemiluminescence (ECL) signal. The reversible Ce(III)/Ce(IV) redox cycle also confers outstanding electrode reusability. As a proof of concept, an immunosensor for selective detection of the cytokine interleukin 6 (IL‐6) was constructed by modifying the outer surface of the SNF. The proposed immunosensor exhibits high sensitivity for IL‐6 detection, achieving a remarkably low detection limit of 2.5 fg mL −1 over a concentration range from 10 fg mL −1 to 10 ng mL −1 . This work offers a promising avenue for expanding the functional scope of SNF‐confined nanozymes in advanced ECL systems for immunosensing.