Pitaya‐Inspired Metal‐Organic Framework Nanozyme for Multimodal Imaging‐Guided Synergistic Cuproptosis, Nanocatalytic Therapy, and Photothermal Therapy

Abstract Nature often provides invaluable insights into technological innovation and the construction of nanomaterials. Inspired by the pitaya fruit's strategy of wrapping seeds within its pulp to enhance seed survival, a unique nanocomposite based on metal‐organic framework (MOF)‐encapsulated CuS nanoparticles (NPs) is developed. This design effectively addresses the challenge of short retention time afforded by CuS NPs for therapeutic and imaging purposes. The MOF acts as the “pitaya pulp” protecting the internal CuS NPs (“pitaya seeds”), thereby increasing their retention time in vivo. This system exhibits triple‐enzyme‐mimicking activities and is proposed for application in photoacoustic and magnetic resonance imaging‐guided therapies, including chemodynamic therapy, photothermal therapy, and cuproptosis‐related therapy. The exceptional enzyme‐mimicking activities of superoxide dismutase, catalase, and peroxidase not only produce oxygen to alleviate hypoxia but also generate a reactive oxygen species (ROS) storm for effective tumor destruction. By combining these multienzymatic properties, superior photothermal performance, and Cu‐induced cuproptosis, nanozyme‐treated mice exhibited an 84% inhibition of tumor growth—approximately double the effect observed in mice treated with CuS NPs alone. This study presents a smart strategy for integrating imaging with therapeutic modalities, achieving exceptional outcomes for precise imaging‐guided tumor therapy.