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The efficacy of sonodynamic therapy (SDT) against GBM is significantly reduced by the expression of apoptosis\u2010inhibitory proteins in GBM cells. In this study, an intelligent nanoplatform (denoted as Aza\u2010BD@PC NPs) based on the aza\u2010boron\u2010dipyrromethene dye and phenyl chlorothionocarbonate\u2010modified DSPE\u2010PEG molecules is developed for synergistic ferroptosis\u2010enabled gas therapy (GT) and SDT of GBM. Once internalized by GBM cells, Aza\u2010BD@PC NPs showed effective cysteine (Cys) consumption and Cys\u2010triggered hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) release for ferroptosis\u2010enabled GT, thereby disrupting homeostasis in the intracellular environment, affecting GBM cell metabolism, and inhibiting GBM cell proliferation. Additionally, the released Aza\u2010BD generated abundant singlet oxygen (<jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub>) under ultrasound irradiation for favorable SDT. In vivo and in vitro evaluations demonstrated that the combined functions of Cys consumption, H<jats:sub>2<\/jats:sub>S production, and <jats:sup>1<\/jats:sup>O<jats:sub>2<\/jats:sub> production induced significant death of GBM cells and markedly inhibited tumor growth, with an impressive inhibition rate of up to 97.5%. Collectively, this study constructed a cascade nanoreactor with satisfactory Cys depletion performance, excellent H<jats:sub>2<\/jats:sub>S release capability, and prominent reactive oxygen species production ability under ultrasound irradiation for the synergistic ferroptosis\u2010enabled GT and SDT of gliomas.<\/jats:p>","DOI":"10.1002\/advs.202309542","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:41:51Z","timestamp":1718325711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Self\u2010Assembled Aza\u2010Boron\u2010Dipyrromethene\u2010Based H<sub>2<\/sub>S Prodrug for Synergistic Ferroptosis\u2010Enabled Gas and Sonodynamic Tumor Therapies"],"prefix":"10.1002","volume":"11","author":[{"given":"Jiajia","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The Second Affiliated Hospital of Anhui Medical University  Hefei 230601 P. R. 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