{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:41:04Z","timestamp":1792784464091,"version":"4.5.0"},"reference-count":43,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"Beijing Life Science Academy","award":["2024100CB0200"],"award-info":[{"award-number":["2024100CB0200"]}]},{"name":"National Basic Research Program of China (973 Program)","award":["2023YFF1205900"],"award-info":[{"award-number":["2023YFF1205900"]}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["22125401 and 22527807"],"award-info":[{"award-number":["22125401 and 22527807"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiomics analysis integrates complementary molecular layers to decode biological complexity; however, the secretome, representing the extracellular and dynamic response of cellular function, remains largely absent from existing multiomics frameworks. Secretome profiling has been constrained by high background interference, poor sensitivity for low-abundance proteins, and perturbations caused by conventional enrichment strategies. Here, we develop a protein corona-based secretome profiling strategy and incorporate it into a multiomics analytical framework. By exploiting the selective adsorption of secreted proteins onto multiple functionalized magnetic nanoparticles under serum-containing and label-free conditions, this method enables the enrichment of secreted proteins under near-physiological conditions. Combining this method with data-independent acquisition (DIA) mass spectrometry enhances identification depth, quantitative dynamic range, and reproducibility. In total, 4,081 protein groups were identified from Michigan Cancer Foundation-7 (MCF-7) cells, including 858 annotated secreted proteins, spanning nearly 5 orders of magnitude in abundance, with &amp;gt;94% consistency across replicates. By integrating secretome profiling with intracellular proteomics and metabolomics, we conducted a multiomics analysis of Tohoku Hospital Pediatrics-1 (THP-1) macrophages across distinct polarization states, revealing differences between M1 and M2 phenotypes in immune activity and metabolic regulation. Notably, polarization-associated variations were more prominent at the secretome level than in intracellular proteomes, highlighting the unique contribution of extracellular protein dynamics to functional state definition. We further applied this strategy to patient-derived organoids (PDOs), enabling secretome profiling in a model that better preserves tumor heterogeneity and microenvironmental context. Collectively, this study establishes a robust and scalable strategy for incorporating the secretome into multiomics analyses.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c00743","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T03:44:37Z","timestamp":1788320677000},"page":"26339-26352","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Protein\nCorona-Based Secretome Profiling Assisting\nCell Multiomics Analysis"],"prefix":"10.1021","volume":"98","author":[{"given":"Caiwei","family":"Hu","sequence":"first","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]},{"name":"Beijing Life Science Academy , ,","place":["Beijing, China, 100089"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Hou","sequence":"additional","affiliation":[{"name":"Beijing Life Science Academy , ,","place":["Beijing, China, 100089"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1542-0297","authenticated-orcid":true,"given":"Yu","family":"Bai","sequence":"additional","affiliation":[{"name":"Peking University , , ,","place":["Beijing, China, 100871"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"issue":"12","key":"2026091511082276200_cit1","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.3390\/genes15121551","article-title":"From Omics\nto Multi-Omics: A Review of Advantages and Tradeoffs","volume":"15","author":"Hayes","year":"2024","journal-title":"Genes"},{"issue":"2","key":"2026091511082276200_cit2","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1128\/MMBR.68.2.207-233.2004","article-title":"Proteomics of protein secretion by Bacillus subtilis:\nseparating the \u201csecrets\u201d of the secretome","volume":"68","author":"Tjalsma","year":"2004","journal-title":"Microbiol. Mol. Biol. Rev."},{"issue":"2","key":"2026091511082276200_cit3","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1586\/14789450.4.2.239","article-title":"Approaches\nto the study of the cell secretome","volume":"4","author":"Hathout","year":"2007","journal-title":"Expert Rev.\nProteomics"},{"issue":"9","key":"2026091511082276200_cit4","doi-asserted-by":"publisher","first-page":"100636","DOI":"10.1016\/j.mcpro.2023.100636","article-title":"An Introduction to\nAnalytical Challenges,\nApproaches, and Applications in Mass Spectrometry-Based Secretomics","volume":"22","author":"Knecht","year":"2023","journal-title":"Mol. Cell. Proteomics"},{"issue":"10","key":"2026091511082276200_cit5","doi-asserted-by":"publisher","first-page":"108826","DOI":"10.1016\/j.celrep.2021.108826","article-title":"Proteomics reveals\ndistinct mechanisms regulating the release of cytokines and alarmins\nduring pyroptosis","volume":"34","author":"Phulphagar","year":"2021","journal-title":"Cell Rep."},{"issue":"10","key":"2026091511082276200_cit6","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1038\/nbt.2356","article-title":"Selective\nenrichment of newly synthesized proteins for quantitative secretome\nanalysis","volume":"30","author":"Eichelbaum","year":"2012","journal-title":"Nat. Biotechnol."},{"issue":"1","key":"2026091511082276200_cit7","doi-asserted-by":"publisher","first-page":"5204","DOI":"10.1038\/s41467-021-25546-y","article-title":"Dynamic\ntracking and identification of tissue-specific secretory proteins\nin the circulation of live mice","volume":"12","author":"Kim","year":"2021","journal-title":"Nat. Commun."},{"issue":"3","key":"2026091511082276200_cit8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2005134118","article-title":"The secretome\nmouse provides a genetic platform to delineate tissue-specific in\nvivo secretion","volume":"118","author":"Liu","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"3","key":"2026091511082276200_cit9","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41589-020-00698-y","article-title":"Cell type-selective\nsecretome profiling in vivo","volume":"17","author":"Wei","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"2026091511082276200_cit10","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1007\/s40242-026-6143-8","article-title":"Serum Small Extracellular Vesicle Proteomic Analysis Based on Functionalized\nNanobowl Enrichment for Screening Candidate Biomarkers of Breast Cancer","volume":"42","author":"Zhao","year":"2026","journal-title":"Chem. Res. Chin. Univ."},{"issue":"7","key":"2026091511082276200_cit11","doi-asserted-by":"publisher","first-page":"2050","DOI":"10.1073\/pnas.0608582104","article-title":"Understanding\nthe nanoparticle-protein corona using methods to quantify exchange\nrates and affinities of proteins for nanoparticles","volume":"104","author":"Cedervall","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"10","key":"2026091511082276200_cit12","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/nnano.2013.181","article-title":"Rapid formation\nof plasma protein corona critically affects nanoparticle pathophysiology","volume":"8","author":"Tenzer","year":"2013","journal-title":"Nat. Nanotechnol."},{"issue":"12","key":"2026091511082276200_cit13","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1038\/nnano.2012.207","article-title":"Biomolecular coronas\nprovide the biological identity of nanosized materials","volume":"7","author":"Monopoli","year":"2012","journal-title":"Nat. Nanotechnol."},{"issue":"7","key":"2026091511082276200_cit14","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.1039\/C1CS15233E","article-title":"Understanding\nand controlling the interaction of nanomaterials\nwith proteins in a physiological environment","volume":"41","author":"Walkey","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"2026091511082276200_cit15","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.colsurfb.2014.06.016","article-title":"Nanoparticle\nsize matters in the formation of plasma protein coronas on Fe3O4 nanoparticles","volume":"121","author":"Hu","year":"2014","journal-title":"Colloids\nSurf. B Biointerfaces"},{"issue":"38","key":"2026091511082276200_cit16","doi-asserted-by":"publisher","first-page":"14265","DOI":"10.1073\/pnas.0805135105","article-title":"Nanoparticle size\nand surface properties determine\nthe protein corona with possible implications for biological impacts","volume":"105","author":"Lundqvist","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"1","key":"2026091511082276200_cit17","doi-asserted-by":"publisher","first-page":"3662","DOI":"10.1038\/s41467-020-17033-7","article-title":"Rapid, deep and precise profiling\nof the plasma proteome\nwith multi-nanoparticle protein corona","volume":"11","author":"Blume","year":"2020","journal-title":"Nat.\nCommun."},{"key":"2026091511082276200_cit18","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/978-3-030-12298-0_3","article-title":"MS-based proteomic\nanalysis of serum and plasma: Problem of high abundant components\nand lights and shadows of albumin removal","volume":"1073","author":"Pietrowska","year":"2019","journal-title":"Adv.\nExp. Med. Biol."},{"issue":"10","key":"2026091511082276200_cit19","doi-asserted-by":"publisher","first-page":"4694","DOI":"10.1021\/acs.jproteome.4c00621","article-title":"Deep profiling of plasma proteoforms\nwith engineered nanoparticles for top-down proteomics","volume":"23","author":"Huang","year":"2024","journal-title":"J. Proteome Res."},{"issue":"2","key":"2026091511082276200_cit20","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1021\/acs.analchem.5c05881","article-title":"Profiling\nglycoproteins enriched by multinanoparticle protein corona","volume":"98","author":"Sutherland","year":"2026","journal-title":"Anal. Chem."},{"issue":"1","key":"2026091511082276200_cit21","doi-asserted-by":"publisher","first-page":"5447","DOI":"10.1038\/s41467-025-60595-7","article-title":"Enrichment\nof extracellular vesicles using Mag-Net for the analysis of the plasma\nproteome","volume":"16","author":"Wu","year":"2025","journal-title":"Nat. Commun."},{"key":"2026091511082276200_cit22","doi-asserted-by":"publisher","first-page":"453","DOI":"10.2741\/2692","article-title":"Macrophage activation\nand polarization","volume":"13","author":"Martinez","year":"2008","journal-title":"Front Biosci."},{"issue":"11","key":"2026091511082276200_cit23","doi-asserted-by":"publisher","first-page":"2351","DOI":"10.1172\/JCI1158","article-title":"Cathepsin\nS activity regulates antigen presentation and immunity","volume":"101","author":"Riese","year":"1998","journal-title":"J. Clin. Invest."},{"issue":"1","key":"2026091511082276200_cit24","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","article-title":"Cysteine cathepsins:\nfrom structure,\nfunction and regulation to new frontiers","volume":"1824","author":"Turk","year":"2012","journal-title":"Biochim.\nBiophys. Acta"},{"issue":"7","key":"2026091511082276200_cit25","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1002\/bies.10300","article-title":"The pleiotropic\nfunctions of the Y-box-binding protein, YB-1","volume":"25","author":"Kohno","year":"2003","journal-title":"BioEssays"},{"issue":"5","key":"2026091511082276200_cit26","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1161\/ATVBAHA.111.222745","article-title":"Apolipoprotein E induces antiinflammatory\nphenotype in macrophages","volume":"31","author":"Baitsch","year":"2011","journal-title":"Arterioscler., Thromb.,\nVasc. Biol."},{"issue":"3","key":"2026091511082276200_cit27","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1097\/MOL.0000000000000507","article-title":"Lysosomal\nacid lipase and lipid metabolism: new mechanisms, new questions, and\nnew therapies","volume":"29","author":"Zhang","year":"2018","journal-title":"Curr. Opin. Lipidol."},{"issue":"6","key":"2026091511082276200_cit28","doi-asserted-by":"publisher","first-page":"440","DOI":"10.18632\/aging.100656","article-title":"Age-related\nincrease of VGF-expression in T lymphocytes","volume":"6","author":"Busse","year":"2014","journal-title":"Aging"},{"key":"2026091511082276200_cit29","doi-asserted-by":"publisher","first-page":"1352946","DOI":"10.3389\/fimmu.2024.1352946","article-title":"Macrophage\npolarization: an important role in inflammatory diseases","volume":"15","author":"Luo","year":"2024","journal-title":"Front. Immunol."},{"issue":"9","key":"2026091511082276200_cit30","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nrendo.2015.117","article-title":"Physiological and pathophysiological roles of NAMPT and NAD metabolism","volume":"11","author":"Garten","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"issue":"1","key":"2026091511082276200_cit31","doi-asserted-by":"publisher","first-page":"11097","DOI":"10.1038\/s41598-022-15482-2","article-title":"Role of GBP1 in innate\nimmunity and potential as a tuberculosis biomarker","volume":"12","author":"Shi","year":"2022","journal-title":"Sci. Rep."},{"issue":"3","key":"2026091511082276200_cit32","doi-asserted-by":"publisher","first-page":"152900","DOI":"10.1016\/j.imbio.2025.152900","article-title":"APOE modulates\nferroptosis to drive macrophage polarization toward the M2 type and\nenhance PTC migration and invasion","volume":"230","author":"Li","year":"2025","journal-title":"Immunobiology"},{"key":"2026091511082276200_cit33","doi-asserted-by":"publisher","first-page":"216457","DOI":"10.1016\/j.canlet.2023.216457","article-title":"A novel role\nof TGFBI in macrophage polarization and macrophage-induced\npancreatic cancer growth and therapeutic resistance","volume":"578","author":"Zhou","year":"2023","journal-title":"Cancer Lett."},{"issue":"5","key":"2026091511082276200_cit34","doi-asserted-by":"publisher","first-page":"109955","DOI":"10.1016\/j.celrep.2021.109955","article-title":"Global characterization\nof macrophage polarization mechanisms and identification of M2-type\npolarization inhibitors","volume":"37","author":"He","year":"2021","journal-title":"Cell Rep."},{"key":"2026091511082276200_cit35","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.3389\/fimmu.2019.01462","article-title":"The Metabolic Signature of Macrophage\nResponses","volume":"10","author":"Viola","year":"2019","journal-title":"Front. Immunol."},{"issue":"1","key":"2026091511082276200_cit36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40364-020-00251-y","article-title":"Metabolic\nreprogramming in macrophage responses","volume":"9","author":"Liu","year":"2021","journal-title":"Biomark.\nRes."},{"issue":"6","key":"2026091511082276200_cit37","first-page":"3147","article-title":"The story of MCF-7\nbreast cancer cell line: 40 years of experience in research","volume":"35","author":"Coms\u0327a","year":"2015","journal-title":"Anticancer Res."},{"issue":"Suppl 2","key":"2026091511082276200_cit38","doi-asserted-by":"publisher","first-page":"S66","DOI":"10.1016\/j.breast.2013.07.012","article-title":"Extracellular\nmatrix components in breast cancer progression and metastasis","volume":"22","author":"Oskarsson","year":"2013","journal-title":"Breast"},{"issue":"3","key":"2026091511082276200_cit39","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.ccell.2019.01.007","article-title":"Integrin signaling in cancer: Mechanotransduction,\nstemness, epithelial plasticity, and therapeutic resistance","volume":"35","author":"Cooper","year":"2019","journal-title":"Cancer Cell"},{"issue":"1","key":"2026091511082276200_cit40","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1038\/s41597-023-02355-0","article-title":"Proteomic\nprofiling across breast cancer cell lines and models","volume":"10","author":"Kalocsay","year":"2023","journal-title":"Sci. Data"},{"issue":"1","key":"2026091511082276200_cit41","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s41392-021-00544-0","article-title":"Extracellular matrix\nand its therapeutic potential\nfor cancer treatment","volume":"6","author":"Huang","year":"2021","journal-title":"Signal Transduction Targeted\nTher."},{"issue":"3","key":"2026091511082276200_cit42","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1172\/JCI90962","article-title":"The role of\nthe complement system in cancer","volume":"127","author":"Afshar-Kharghan","year":"2017","journal-title":"J. Clin. Invest."},{"issue":"9","key":"2026091511082276200_cit43","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1016\/j.chembiol.2017.06.012","article-title":"Tumor organoids\nas a pre-clinical cancer model for drug discovery","volume":"24","author":"Weeber","year":"2017","journal-title":"Cell Chem. Biol."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.6c00743","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26339\/67599723\/acs.analchem.6c00743.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/98\/36\/26339\/67599723\/acs.analchem.6c00743.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:53:29Z","timestamp":1789487609000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/98\/36\/26339\/5348766\/A-Novel-Protein-Corona-Based-Secretome-Profiling"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,28]]},"references-count":43,"journal-issue":{"issue":"36","published-online":{"date-parts":[[2026,8,28]]},"published-print":{"date-parts":[[2026,9,15]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.6c00743","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,28]]}}}