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Here, we develop nanostructured magnetic particles (NMPs) exhibiting highly sensitive and specific circulating tumor cells (CTCs) quantification enabled by Fo\u0308rster resonance energy transfer (FRET), and demonstrate precise diagnosis of PC from benign pancreatic tumors (BPT) and healthy donors (HD). The NMPs are modified with aptamer, which can preferably bind to cells with higher specificity and guarantee effective substitution of acceptors. Compared with smooth magnetic particles (SMPs), NMPs provide more binding sites for CTCs, which significantly enhances the fluorescent signal and detection limit. An ultralow detection limit (1 cell\/mL) is achieved using this unique capture and detection platform. Clinical validation demonstrates the superior diagnostic performance of this CTCs-based approach, with 91.7% sensitivity in detecting PC patients and 96.6% specificity. Receiver operating characteristic (ROC) analysis reveals an area under the curve (AUC) of 0.957, outperforming conventional biomarkers (CA19\u20139:0.905; CEA: 0.747; CA125:0.625). Our strategy represents an important methodological progress for tumor liquid biopsy, showing promise for clinical diagnosis, monitoring, and evaluation.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c02175","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:35:58Z","timestamp":1784140558000},"page":"21536-21545","source":"Crossref","is-referenced-by-count":1,"title":["Aptamer-Modified\nNanostructured Particles Exhibiting\nSensitive Cell-Scale FRET Enable Precise Pancreatic Cancer Diagnosis"],"prefix":"10.1021","volume":"98","author":[{"given":"Na","family":"He","sequence":"first","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Capital Medical University , , ,","place":["Beijing, P. R. China, 100050"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuemeng","family":"Yang","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Miao","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilin","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100190"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, P. R. China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Duan","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100190"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, P. R. China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Shen","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100190"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, P. R. China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2683-7963","authenticated-orcid":true,"given":"Li-Ping","family":"Xu","sequence":"additional","affiliation":[{"name":"University of Science and Technology Beijing , , ,","place":["Beijing, P. R. China, 100083"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-2428","authenticated-orcid":true,"given":"Yongyang","family":"Song","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100190"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, P. R. China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2559-5181","authenticated-orcid":true,"given":"Shutao","family":"Wang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, P. R. China, 100190"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, P. R. 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Des."},{"key":"2026072808073278600_cit28","doi-asserted-by":"publisher","first-page":"19742","DOI":"10.1021\/acsnano.4c05280","article-title":"Portable\nnear-infrared to near-infrared platform for homogeneous\nquantification of biomarkers in complex biological samples","volume":"18","author":"Li","year":"2024","journal-title":"ACS Nano"},{"key":"2026072808073278600_cit29","doi-asserted-by":"publisher","first-page":"1802266","DOI":"10.1002\/smll.201802266","article-title":"Quantum dot-based\nFRET immunoassay for HER2 using ultrasmall\naffinity proteins","volume":"14","author":"Wu","year":"2018","journal-title":"Small"},{"key":"2026072808073278600_cit30","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202113617","article-title":"A dual-color fluorescent probe allows simultaneous\nimaging of main and papain-like proteases of SARS-CoV-2-infected cells\nfor accurate detection and rapid inhibitor screening","volume":"61","author":"Cheng","year":"2022","journal-title":"Angew. Chem., Int. 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Drug Delivery Rev."},{"key":"2026072808073278600_cit39","doi-asserted-by":"publisher","first-page":"8469","DOI":"10.1021\/acsnano.9b04378","article-title":"Extending single-molecule\nFo\u0308rster Resonance\nEnergy Transfer (FRET) range beyond 10 nm in zero-mode waveguides","volume":"13","author":"Baibakov","year":"2019","journal-title":"ACS Nano"},{"key":"2026072808073278600_cit40","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1038\/s41566-024-01384-4","article-title":"Super-resolved\nFRET and co-tracking\nin pminflux","volume":"18","author":"Cole","year":"2024","journal-title":"Nat. Photonics"},{"key":"2026072808073278600_cit41","doi-asserted-by":"publisher","first-page":"11878","DOI":"10.1021\/acs.analchem.1c02833","article-title":"Aggregation-enhanced\nenergy transfer for mitochondria-targeted ATP ratiometric imaging\nin living cells","volume":"93","author":"Li","year":"2021","journal-title":"Anal. 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Soc."},{"key":"2026072808073278600_cit43","doi-asserted-by":"publisher","first-page":"5779","DOI":"10.1038\/s41467-023-41053-8","article-title":"Heterostructure\nparticles enable omnidispersible in\nwater and oil towards organic dye recycle","volume":"14","author":"Song","year":"2023","journal-title":"Nat.\nCommun."},{"key":"2026072808073278600_cit44","doi-asserted-by":"publisher","first-page":"2217","DOI":"10.1021\/acs.analchem.3c05287","article-title":"Intracellular microRNA\nimaging and specific discrimination of prostate cancer circulating\ntumor cells using multifunctional gold nanoprobe-based thermophoretic\nassay","volume":"96","author":"Luo","year":"2024","journal-title":"Anal. 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