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One promising strategy to improve anticancer immune responses is to induce immunogenic cell death (ICD) in tumor cells. However, currently available ICD\u2010inducing agents are limited by several factors, including homogeneous mechanisms of action, low induction efficiency, and complex preparation or administration procedures. To improve ICD induction, particularly in immunologically \u201ccold\u201d tumors, this study proposes a drug co\u2010delivery system designed to achieve effective chemotherapy and multi\u2010pathway ICD induction, thereby enhancing antitumor immunity and improving the efficacy of chemoimmunotherapy. Specifically, a poly(podophyllotoxin)\u2010based polymer was engineered to encapsulate the carbon monoxide (CO) prodrug COP, followed by surface modification with D\u2010\u03b1\u2010tocopheryl polyethylene glycol succinate, a stabilizing agent that promotes reactive oxygen species (ROS) generation. This design yielded a ROS cascade\u2010amplified drug delivery platform for chemoimmunotherapy. Damage\u2010associated molecular patterns (DAMPs) were released when ROS, CO, and podophyllotoxin combined to trigger ICD in cancer cells. Subsequently, these DAMPs facilitated the activation and maturation of dendritic cells, which then attracted\u00a0cytotoxic T lymphocytes, thereby amplifying antitumor immune responses and improving treatment results.<\/jats:p>","DOI":"10.1002\/adhm.71279","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:21:58Z","timestamp":1780546918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ROS Cascade\u2010Amplified Polymeric Nanosystem Exhibiting Multi\u2010Pathway Induction of Immunogenic Cell Death and Chemotherapeutic Efficacy in Tumor"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9491-1953","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Scientific Research Center Department of Thoracic Surgery The Seventh Affiliated Hospital Sun Yat\u2010sen University  Shenzhen P. R. 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