Yijun Zhang, Shiyi Gong, Xianglin Gao, J. Chi, Jipei Lu, Bo Liang, Haojie Yu, Feilong Dong, TT Li, Weiting Yu, Lei Zhang
Nanozyme-based catalytic therapy has emerged as a promising antitumor strategy by leveraging endogenous substrates to generate reactive oxygen species (ROS) and induce oxidative damage in tumors. However, its efficacy is often constrained by inadequate catalytic activity and inefficient in vivo delivery, largely due to the complex tumor microenvironment. To overcome these limitations, we developed a dual-atom nanozyme (DA nanozyme) with precisely paired Fe-Co bimetallic active sites, which exhibits significantly enhanced multienzyme mimetic activities─including oxidase-like (OXD), peroxidase-like (POD), and catalase-like (CAT) functions and glutathione (GSH) depletion. This synergistic catalytic action amplifies oxidative stress and promotes tumor cell death. Furthermore, a biodegradable composite microneedle (MN) patch was engineered for localized delivery of the FeCo DA nanozyme directly to subcutaneous tumor sites. By integrating multienzyme catalysis with near-infrared photothermal therapy, this platform effectively inhibits hepatocellular carcinoma growth and achieves complete tumor eradication in vivo. Collectively, this work provides an innovative and translatable strategy for synergistic antihepatoma therapy through rational nanozyme design and precision tumor-localized delivery.