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Matrix\u2010assisted laser desorption\/ ionization mass spectrometry (MALDI\u2010MS) has emerged as a promising platform for metabolic profiling, but its capability is hindered by the limited light absorption and energy transfer of conventional matrix materials. In this work, a high\u2010efficiency metabolic detection platform based on high\u2010entropy oxide particles (mHEO) with an interconnected mesoporous structure and tailored compositions is established. Owing to their abundant active sites and excellent light utilization efficiency, the mHEO particles show significantly improved photothermal and photochemical properties with an eightfold localized enhanced electromagnetic field and higher surface temperatures (616\u00a0\u00b0C) than nonporous HEOs (336\u00a0\u00b0C). As a result, MALDI\u2010MS based on the mHEO matrix exhibits high sensitivity, good reproducibility (Coefficient of Variation &lt; 10%), and ultralow detection limits with 1\u20133 orders of magnitude lower than their endogenous concentrations. Furthermore, the mHEO\u2010based MALDI\u2010MS platform is applied to analyze paired arterial\/venous blood samples from pancreatic cancer (PC) patients with the assistance of machine learning. Four tumor microenvironment\u2010associated metabolites are identified as a potential biomarker panel of PC, achieving a robust pancreas\u2010venous plasma classification, which allows the timely screening and targeted treatment of PC.<\/jats:p>","DOI":"10.1002\/adma.202513988","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:17:01Z","timestamp":1764944221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mesoporous High\u2010Entropy Oxides Nanoplatform Decodes Paired\u2010Plasma Metabolic Fingerprinting of Pancreatic Cancer"],"prefix":"10.1002","volume":"38","author":[{"given":"Yue","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Chemistry Shanghai Stomatological Hospital &amp; School of Stomatology State Key Laboratory of Molecular Engineering of Polymers Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Fudan University  Shanghai 200433 P. 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