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To overcome the challenges of residual tumor cells and postoperative immune resistance, an injectable hydrogel is developed that co\u2010delivers propranolol (Pro) and imiquimod (IMQ). The rationale is to achieve a synergistic therapeutic effect by enhancing immunogenic cell death (ICD) and strengthening antitumor immunity. The hydrogel is synthesized via boronate ester crosslinking between HA\u2010EGCG and CMCS\u2010PBA and demonstrates excellent injectability, self\u2010healing, biodegradability, and tissue adhesion. In vitro, Pro potentiated IMQ\u2010induced reactive oxygen species (ROS) production, enhancing ICD markers such as calreticulin exposure (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP) release, thereby promoting dendritic cell maturation and T cell activation. In vivo, Pro\/IMQ@ Hydrogel (PIH) effectively inhibited tumor recurrence in an incomplete melanoma resection model, significantly reducing tumor volume and inducing apoptosis without systemic toxicity. Immunohistochemical analyses revealed increased CD8\u207a and CD4\u207a T cell infiltration, elevated inflammatory cytokine levels, and enhanced memory T cell responses. This work highlights the potential of PIH as a potent localized chemo\u2010immunotherapy platform for melanoma by converting \u201ccold\u201d tumors into \u201chot\u201d immunogenic lesions.<\/jats:p>","DOI":"10.1002\/adhm.202503019","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:45:19Z","timestamp":1761205519000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Injectable Hydrogel Co\u2010Delivering Propranolol and Imiquimod to Synergistically Enhance Immunogenic Cell Death after Melanoma Resection"],"prefix":"10.1002","volume":"15","author":[{"given":"Yunfeng","family":"Tang","sequence":"first","affiliation":[{"name":"Head and Neck Oncology Ward Cancer Center West China Hospital Cancer Center Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangtian","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Orthopedics Research Institute West China Hospital Sichuan University  Chengdu 610041 China"},{"name":"Trauma Medical Center Department of Orthopedics Surgery West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Orthopedics Research Institute West China Hospital Sichuan University  Chengdu 610041 China"},{"name":"Trauma Medical Center Department of Orthopedics Surgery West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Orthopedics Research Institute West China Hospital Sichuan University  Chengdu 610041 China"},{"name":"Trauma Medical Center Department of Orthopedics Surgery West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Biomaterials Sichuan University  Chengdu Sichuan 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0713-9035","authenticated-orcid":false,"given":"Renliang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Orthopedics Research Institute West China Hospital Sichuan University  Chengdu 610041 China"},{"name":"Trauma Medical Center Department of Orthopedics Surgery West China Hospital Sichuan University  Chengdu 610041 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2024.09.035"},{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-004668","volume":"10","author":"Bhave P.","year":"2022","journal-title":"J. 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