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Currently, no effective therapeutic strategies can improve the prognosis of pancreatic cancer. The activation of quiescent pancreatic stellate cells (PSCs) and their crosstalk with pancreatic cancer cells (PCCs) lead to the formation of a fibrotic physical barrier and an immunosuppressive tumor microenvironment (TME), which severely impede drug delivery and penetration. To improve PC treatment, a dual\u2010targeting strategy capable of simultaneously acting on PCCs and PSCs is urgently needed to revert activated PSCs (aPSCs) to their quiescent state and suppress the proliferation of PCCs. KPT\u20106566, a small\u2010molecule inhibitor, shifts PSCs from an activated to a quiescent state, reprograms the tumor immune microenvironment (TIME) to enhance anti\u2010PD\u2010L1 immunotherapy efficacy, suppresses PCCs proliferation, and induces PD\u2010L1 expression on PCC surfaces, thereby increasing sensitivity to PD\u2010L1\u2010targeted therapies. This study designs two amphiphilic peptides, C16\u2010LLGG\u2010COO\u2010\n                    <jats:sup>D<\/jats:sup>\n                    PPA\u20101(DPPA\u20101@PA) and DSPE\u2010PEG\u2010NHS\u2010CGKRK(CGKRK@PA), which can co\u2010assemble to encapsulate KPT\u20106566 and finally form a peptide\u2010based nanoparticle termed DP\u2010KPT\u2010CG@PA. This nanoparticle precisely targets PCCs and PSCs to co\u2010deliver KPT\u20106566, while synergizing with a PD\u2010L1\u2010blocking peptide to initiate immune checkpoint blockade therapy, thereby enhancing response rates to pancreatic cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202503114","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T12:44:51Z","timestamp":1758717891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting PIN1 in Pancreatic Tumor Microenvironment with Peptide Amphiphiles Unleashes Immune Checkpoint Therapy"],"prefix":"10.1002","volume":"15","author":[{"given":"Yuanyuan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery I General Surgery Center Zhujiang Hospital Southern Medical University  Guangzhou China"},{"name":"Institute of Digital Intelligent Minimally Invasive Surgery 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