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Here, we report a lanthanide metal\u2013organic framework (Ln\u2010MOF) functionalized with boronic acid and carboxylate dual ligands, which captures exosomal proteins via synergistic phosphate coordination, boronate\u2010diol complexation, and cation\u2010\u03c0 interactions. Compared with traditional ultracentrifugation, which identifies 1003 proteins from 200 \u00b5L of plasma, the Ln\u2010MOF method identifies 1523 proteins from only 50 \u00b5L of plasma. Notably, the method enriches glycoproteins and phosphoproteins by 2.1\u2010fold and 1.8\u2010fold, respectively. Applying this platform to pancreatic ductal adenocarcinoma (PDAC) patients and healthy controls, we delineate tumor tissue hypermetabolism vs. systemic immune suppression.<\/jats:p>","DOI":"10.1002\/smll.76296","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:37:13Z","timestamp":1792132633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasensitive Trace Sample Proteomics for Pancreatic Ductal Adenocarcinoma Diagnosis Empowered by Dual\u2010Affinity Spherical Ln\u2010MOFs"],"prefix":"10.1002","author":[{"given":"Ruizhi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Radiology Huadong Hospital Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery Hepato\u2010Biliary\u2010Pancreatic Surgery Huadong Hospital Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9667-0878","authenticated-orcid":false,"given":"Wangwang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Hepato\u2010Biliary\u2010Pancreatic Surgery Huadong Hospital Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7359-8873","authenticated-orcid":false,"given":"Zhiwei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of General Surgery Hepato\u2010Biliary\u2010Pancreatic Surgery Huadong Hospital Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1549-3499","authenticated-orcid":false,"given":"Xianting","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Surgical Intensive Care Unit Xinhua Hospital School of Medicine and School of Biomedical Engineering Shanghai Jiao Tong University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongyi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Hepato\u2010Biliary\u2010Pancreatic Surgery Huadong Hospital Fudan University  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202107712","article-title":"Penetrating Micelle for Reversing Immunosuppression and Drug Resistance in Pancreatic Cancer Treatment","volume":"18","author":"Chen Q.","year":"2022","journal-title":"Small"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3390\/ph14080740","article-title":"Epithelial to Mesenchymal Transition in Patients with Pancreatic Ductal Adenocarcinoma: State\u2010of\u2010the\u2010Art and Therapeutic Opportunities","volume":"14","author":"Dardare J.","year":"2021","journal-title":"Pharmaceuticals"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"556","DOI":"10.3892\/ol.2025.15302","article-title":"Serum Fucosylated Receptor Expression Enhancing Protein 5 As A Biomarker For Early Stage Pancreatic Cancer","volume":"30","author":"Sogawa K.","year":"2025","journal-title":"Oncology Letters"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202513668","article-title":"Molecular Probes for Pancreatic Cancer Diagnosis: Recent Advances and Further Perspectives","volume":"22","author":"Li J.","year":"2026","journal-title":"Small"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1200\/JCO.2017.77.6658","article-title":"Serum Biomarker Signature\u2010Based Liquid Biopsy for Diagnosis of Early\u2010Stage Pancreatic Cancer","volume":"36","author":"Mellby L. 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