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However, very few direct ultrasound\u2010responsive redox systems are applicable under therapeutic ultrasound (1\u00a0MHz). Herein, the investigations on nanoprodrug of DHE@PEG\u2010SS\u2010DSPE are reported, which exhibit glutathione\u2010activated release of dihydroethidium (DHE) in tumor cells. DHE is stable with good biosafety and is transformed into cytotoxic ethidium to induce DNA damage under medical ultrasound irradiation, accompanied by the generation of reactive oxygen species. Further, DHE@PEG\u2010SS\u2010DSPE could effectively induce ferroptosis through glutathione depletion, lipid peroxide accumulation, and downregulation of glutathione peroxidase 4. In vivo studies confirmed that DHE@PEG\u2010SS\u2010DSPE nanoparticles effectively inhibit both the growth of solid tumors and the expression of metastasis\u2010related proteins in mice, thus effectively inhibiting lung metastasis. This DHE\u2010based prodrug nanosystem could lay a foundation for the design of ultrasound\u2010driven therapeutic agents.<\/jats:p>","DOI":"10.1002\/adma.202308205","type":"journal-article","created":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T11:21:07Z","timestamp":1696418467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["An Activatable Prodrug Nanosystem for Ultrasound\u2010Driven Multimodal Tumor Therapy and Metastasis Inhibition"],"prefix":"10.1002","volume":"35","author":[{"given":"Jiazhu","family":"Zheng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology  Dalian 116024 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoying","family":"Ge","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Fine Chemicals Frontiers 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