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Therapeutic agents with different functions, including FOLFIRINOX (FFX), surufatinib (SUR), and anti\u2010PD\u20101 (\u03b1PD\u20101), are co\u2010administered to tumors in animal models using microneedle (MN) patches to achieve site\u2010targeted synergistic efficacy. The core\u2013shell MN structure is used, with the outer layer providing rapid FFX delivery and the inner layer providing sustained release of SUR and \u03b1PD\u20101. Compared with intratumoral drug injection and traditional systemic administration, MN patch\u2010mediated administration markedly suppresses tumor growth and liver metastasis at lower doses, reduces systemic drug exposure and toxicity, and prolongs intratumoral drug retention. In addition, the MN patch\u2010mediated intratumoral co\u2010delivery reshapes the TME by boosting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells infiltration, inhibiting Foxp3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory T cells, and reducing CD206\n                    <jats:sup>+<\/jats:sup>\n                    tumor\u2010associated macrophages infiltration, resulting in downregulation of tumor epithelial\u2010mesenchymal transition and increased tumor cell apoptosis. In summary, MN patch\u2010mediated delivery of therapeutic agents provides sufficient intratumoral doses and minimizes systemic toxicity through multiple microchannels, suggesting that MN patch co\u2010delivery is a promising adjunct for enhancing efficacy against PDAC.\n                  <\/jats:p>","DOI":"10.1002\/advs.76478","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:23:14Z","timestamp":1783945394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Spatially Directed Microneedle Patch Enables Intratumoral Co\u2010Delivery of FOLFIRINOX, Surufatinib, and Anti\u2010PD\u20101 for Chemo\u2010Immunotherapy of Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Tingting","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Pancreatic Surgery Shanghai Key Laboratory of Pancreatic Disease Shanghai General Hospital 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