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Remarkably,\u00a0ZIF8\u00a0in response to\u00a0tumor microenvironment\u00a0enhances drug targeting and protects drugs from premature degradation. Meanwhile, the Pt<jats:sup>IV<\/jats:sup>\u00a0center can be easily reduced\u00a0to\u00a0cisplatin because of the large amount of GSH, thus liberating the triptolide as the coordinated ligand. The released\u00a0cisplatin and hemin in turn boost the tumor cell \u201c1+1\u201d apoptosis through chemotherapy and photodynamic therapy, respectively. Furthermore, GSH reduction through\u00a0Pt<jats:sup>IV<\/jats:sup>\u00a0weakens the activation of glutathione peroxidase 4 (GPX4) effectively. The released triptolide can inhibit the expressions of GSH by regulating nuclear factor E2 related factor 2 (Nrf2), further promoting membrane lipid peroxidation, thus \u201c1+1\u201d\u00a0ferroptosis can be achieved. Both\u00a0in\u00a0vitro\u00a0and\u00a0in\u00a0vivo\u00a0results demonstrate that the nanosystem can not only perform superior specificity and therapeutic outcomes but also reduce\u00a0the toxicity to normal cells\/tissues of cisplatin and triptolide effectively. Overall, the prodrug\u2010based smart system provides an efficient therapeutic strategy for cancer treatment by virtue of the effect of enhanced \u201c1+1\u201d apoptosis and \u201c1+1\u201d ferroptosis therapies.<\/jats:p>","DOI":"10.1002\/adhm.202301328","type":"journal-article","created":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T06:04:55Z","timestamp":1688191495000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A Dual Stimuli\u2010Responsive Nanoplatform Loaded Pt<sup>IV<\/sup>\u2010Triptolide Prodrug for Achieving Synergistic Therapy toward Breast Cancer"],"prefix":"10.1002","volume":"12","author":[{"given":"Kang","family":"Fang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Chemical Assessment and Sustainability School of Chemical Science and Engineering. 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