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However, their clinical application is hindered by insufficient efficiency in inducing immunogenic cancer cell death (ICD) and systemic inflammation caused by immune adjuvants. Here, personalized cancer vaccines are constructed in situ for melanoma immunotherapy based on bioorthogonal catalytic microneedles, which enable the catalytic release of prodrugs at tumor sites and mediate strong ICD and an enhanced tumor immune response while avoiding systemic immune storms and toxic side effects. By incorporating TiO\n                    <jats:sub>2<\/jats:sub>\n                    nanosheets supported Pd into swellable microneedles, the bioorthogonal microneedles are constructed to catalyze the depropargylation reaction of doxorubicin (DOX) prodrug and imiquimod (IMQ) prodrug in situ. The activated DOX at subcutaneous tumor sites induced strong ICD and released tumor\u2010associated antigens. Concurrently, the activated IMQ acts as a Toll\u2010like receptor (TLR7) agonist, enhancing the anti\u2010tumor immune response. In vivo experiments demonstrate that this immunotherapy achieves \u224897% inhibition of primary tumors and effectively inhibits untreated distant tumors (\u224894% inhibition) and lung metastasis (\u224892% inhibition).\n                  <\/jats:p>","DOI":"10.1002\/smll.202500015","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T05:49:54Z","timestamp":1743054594000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Construction of In Situ Personalized Cancer Vaccines by Bioorthogonal Catalytic Microneedles for Augmented Melanoma Immunotherapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Qian\u2010He","family":"Xu","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials School of Chemistry and Molecular Engineering East China University of Science &amp; Technology  Shanghai 200237 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu\u2010Yuan","family":"Yin","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Functional Materials Chemistry Key Laboratory for Advanced Materials School of Chemistry and Molecular Engineering East China University of Science &amp; 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