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Published on: March 18, 2014
Injectable Cu2+ loaded rhein hydrogel for cross-amplifying osteosarcoma apoptosis and cuproptosis
Jianwei Zhu1, Tingyiwen Zhou2, Xiaopeng Tang2
1Department of Biochemistry, Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, School of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu, 210023, China; Department of Diagnostic Radiology, Yong Loo Lin School of, National University of Singapore, 119074, Singapore.
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Osteosarcoma (OS) remains a formidable clinical challenge due to its aggressive nature, early metastasis, and resistance to conventional therapies. Here, we report an injectable Cu2+-loaded rhein hydrogel (RCugel) that integrates sonodynamic therapy (SDT) and cuproptosis with RNA epitranscriptomical regulation for OS treatment. After administration, RCugel released Cu2+ and rhein to trigger cuproptosis and generated singlet oxygen to induce apoptosis under sonication, respectively. Concurrently, Cu2+ produced additional ROS to amplify apoptosis by reacting with intracellular GSH via a Fenton-like reaction while rhein downregulated ATP7B levels via inhibiting "FTO/DACT1/β-catenin/ATP7B″ axis to further amplify cuproptosis efficiency. Collectively, our study demonstrates that RCugel's synergistic induction of crossing amplification between apoptosis and cuproptosis via epitranscriptomic remodeling represents a potent, translational strategy for improving osteosarcoma therapy.
