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Although arsenic trioxide (ATO) can restore transcriptional activity of structural p53 mutants, its clinical application is limited by subtype selectivity and systemic toxicity. In parallel, p53 deficiency creates dependence on S\/G2 checkpoints, rendering ATR a synthetic lethal target; however, allicin, a natural ATR inhibitor and hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) donor, suffers from poor stability and bioavailability. Here, we developed a liposomal nanomedicine co\u2010delivering pro\u2010ATO (As\n                    <jats:sup>5+<\/jats:sup>\n                    ) and allicin (AsAcP@LP) to integrate mutant p53 reactivation with DDR\u2010targeted synthetic lethality. This formulation improves drug stability, pharmacokinetics, and tumor accumulation while masking allicin's odor. Upon tumor\u2010specific release, allicin\u2010mediated redox activation converts As\n                    <jats:sup>5+<\/jats:sup>\n                    to cytotoxic As\n                    <jats:sup>3+<\/jats:sup>\n                    , enabling selective p53 reactivation, concurrent ATR inhibition, and H\n                    <jats:sub>2<\/jats:sub>\n                    S\u2010amplified apoptosis. AsAcP@LP exhibits synergistic antitumor efficacy with favorable tolerability, providing a rational nanotherapeutic strategy for p53\u2010mutant cancers.\n                  <\/jats:p>","DOI":"10.1002\/advs.202519194","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T20:09:27Z","timestamp":1769717367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pro\u2010ATO\/Allicin Liposomes for Dual\u2010Pathway Targeting of p53\u2010Mutant Tumors"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiaoling","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Shanghai Pulmonary Hospital  Tongji University School of Medicine Shanghai China"},{"name":"Zhejiang Provincial Key Laboratory of Diagnosis and Treatment of Thoracic Cancer  Hangzhou Zhejiang 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Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JingQuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences The First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LiTing","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences The First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences The First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang China"},{"name":"Department of Dermatology &amp; Cosmetology The First Affiliated Hospital of Zhejiang Chinese Medical University  Hangzhou Zhejiang 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