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Inspired by the pitaya fruit's strategy of wrapping seeds within its pulp to enhance seed survival, a unique nanocomposite based on metal\u2010organic framework (MOF)\u2010encapsulated 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 \u201cpitaya pulp\u201d protecting the internal CuS NPs (\u201cpitaya seeds\u201d), thereby increasing their retention time in vivo. This system exhibits triple\u2010enzyme\u2010mimicking activities and is proposed for application in photoacoustic and magnetic resonance imaging\u2010guided therapies, including chemodynamic therapy, photothermal therapy, and cuproptosis\u2010related therapy. The exceptional enzyme\u2010mimicking 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\u2010induced cuproptosis, nanozyme\u2010treated mice exhibited an 84% inhibition of tumor growth\u2014approximately 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\u2010guided tumor therapy.<\/jats:p>","DOI":"10.1002\/adhm.202402915","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T05:59:18Z","timestamp":1729663158000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Pitaya\u2010Inspired Metal\u2010Organic Framework Nanozyme for Multimodal Imaging\u2010Guided Synergistic Cuproptosis, Nanocatalytic Therapy, and Photothermal Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Quer","family":"Yue","sequence":"first","affiliation":[{"name":"State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance in Wuhan Wuhan Institute of Physics and Mathematics Innovation Academy for Precision Measurement Science and Technology Chinese Academy of Sciences  Wuhan 430071 P. 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