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Through a high\u2010throughput screen of 2,500 FDA\u2010approved drugs using a three\u2010dimensional tumor organoid platform, we identified thonzonium bromide (THO) as an inducer of gasdermin D (GSDMD)\u2010mediated pyroptosis, which results in the release of damage\u2010associated molecular patterns (DAMPs) to activate antitumor immunity. To achieve targeted delivery, we designed a core\u2013shell\u2010structured biomimetic nanoparticle (THO\/AMT\u2010si NP) consisting of a core formed by tetrahedral DNA (TDN NPs) constructed using DNA origami technology, which is loaded with THO and P\u2010gp siRNA, and an outer layer coated with a programmatically designed hybrid membrane (AREP). These findings indicate that THO\/AMT\u2010Si NPs can effectively target TNBC tumors, convert \u201ccold\u201d tumors into \u201chot\u201d tumors by inducing pyroptosis in cancer cells, reverse immune cell exhaustion, and simultaneously overcome cancer cell multidrug resistance, thereby achieving synergistic inhibition of tumor growth and metastasis. In summary, this biomimetic nanomedicine enhances immunotherapy for TNBC by combining synergistic cascade targeting, immune checkpoint blockade, and thermosis\u2010mediated immune activation.<\/jats:p>","DOI":"10.1002\/anie.7162372","type":"journal-article","created":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T12:12:06Z","timestamp":1788005526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Engineering\u2010Editable Hybrid Membrane\u2011Camouflaged DNA Origami Drug Enables Checkpoint Blockade and Immune Activation for Triple\u2010Negative Breast Cancer Immunotherapy"],"prefix":"10.1002","volume":"65","author":[{"given":"Xiaqing","family":"Gong","sequence":"first","affiliation":[{"name":"School of Pharmacy Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmacy Anhui 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