{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:05:15Z","timestamp":1787508315617,"version":"build-2736575974"},"reference-count":244,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Liaocheng Municipal Bureau of Science and Technology, High-talented Foreign Expert Introduction Program","award":["GDWZ202401"],"award-info":[{"award-number":["GDWZ202401"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Extracellular vesicles (EVs), particularly exosomes, have emerged as critical mediators of intercellular communication, yet the metabolite fraction of their cargo remains substantially underexplored relative to proteins and nucleic acids. This review synthesizes current knowledge on the exosomal metabolome as a functionally distinct intercellular signaling system with unique biophysical properties. We review the mechanisms proposed to govern metabolite encapsulation into exosomes, encompassing membrane transporter involvement, lipid raft partitioning, and binding to luminal proteins, and discuss the unresolved question of whether metabolite loading is selective or stochastic. Critically, we present a quantitative framework evaluating whether delivered metabolite quantities are sufficient to alter recipient cell metabolic pools, distinguishing receptor-mediated signaling from bulk substrate delivery. We also address methodological considerations including contamination artifacts and isolation-method biases that complicate interpretation of EV metabolomics data. Exosomal metabolites are reviewed across four functional categories: energy substrates (ATP, lactate, amino acids), signaling molecules (TCA cycle intermediates, eicosanoids, nucleotides), redox cofactors and antioxidants (NADH, glutathione), and oncometabolites. For each category, available evidence is critically appraised, distinguishing metabolites with direct mass spectrometric detection from those whose roles are inferred from parent-cell biology. The review examines the roles of exosomal metabolites in tumor-stroma metabolic symbiosis, immunometabolic regulation, inter-organ crosstalk in metabolic diseases including type 2 diabetes and non-alcoholic fatty liver disease, cancer metastasis, viral infections, and immune evasion. A quantitative framework is discussed to evaluate whether delivered metabolite quantities are sufficient to alter recipient cell metabolic pools, distinguishing receptor-mediated signaling from bulk substrate delivery. Technical challenges in exosomal metabolomics are reviewed, including the impact of isolation method on data quality, contamination artifacts, and current standardization gaps. Therapeutic implications of exosomal metabolite signaling are discussed, encompassing metabolite-loaded exosomes as therapeutic vehicles and exosomal metabolite loading as a pharmacological target. Integration of single-vesicle technologies with systems biology approaches is highlighted as a promising direction for advancing this field toward precision medicine applications in oncological and metabolic disorders.<\/jats:p>","DOI":"10.3390\/metabo16030207","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T10:49:58Z","timestamp":1774003798000},"page":"207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Extracellular Vesicles Associated Metabolites as Intercellular Signalling Mediators in Disease and Therapy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0268-1167","authenticated-orcid":false,"given":"Abdul","family":"Qadeer","sequence":"first","affiliation":[{"name":"School of Medical Sciences, Shandong Xiehe University, Jinan 250109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6839-7849","authenticated-orcid":false,"given":"Abd","family":"Ullah","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-2996","authenticated-orcid":false,"given":"Muhammad Zahoor","family":"Khan","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-2069","authenticated-orcid":false,"given":"Khalaf F.","family":"Alsharif","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6930-5214","authenticated-orcid":false,"given":"Fuad M.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6688-0106","authenticated-orcid":false,"given":"Khalid J.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0924-2706","authenticated-orcid":false,"given":"Abdulwahab A.","family":"Abuderman","sequence":"additional","affiliation":[{"name":"Basic Medical Sciences Department, College of Medicine, Prince Sattam Bin Abdulaziz University, Alkharj 16273, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaau6977","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"268","DOI":"10.7150\/thno.47021","article-title":"Cardiac telocytes inhibit cardiac microvascular endothelial cell apoptosis through exosomal miRNA-21-5p-targeted cdip1 silencing to improve angiogenesis following myocardial infarction","volume":"11","author":"Liao","year":"2021","journal-title":"Theranostics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e13904","DOI":"10.1111\/cts.13904","article-title":"Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes","volume":"17","author":"Wang","year":"2024","journal-title":"Clin. Transl. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/s41423-025-01323-5","article-title":"The role of exosomes in immunopathology and potential therapeutic implications","volume":"22","author":"Wang","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"20240292","DOI":"10.1098\/rstb.2024.0292","article-title":"Before LUCA: Unearthing the chemical roots of metabolism","volume":"380","author":"Carbonell","year":"2025","journal-title":"Philos. Trans. B"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Schoenmakers, L.L., Reydon, T.A., and Kirschning, A. (2024). Evolution at the Origins of Life?. Life, 14.","DOI":"10.3390\/life14020175"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7708","DOI":"10.1021\/acs.chemrev.0c00191","article-title":"Nonenzymatic metabolic reactions and life\u2019s origins","volume":"120","author":"Muchowska","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Williams, C., Palviainen, M., Reichardt, N.-C., Siljander, P.R.-M., and Falc\u00f3n-P\u00e9rez, J.M. (2019). Metabolomics applied to the study of extracellular vesicles. Metabolites, 9.","DOI":"10.3390\/metabo9110276"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8314","DOI":"10.1021\/acs.analchem.8b01726","article-title":"High-performance chemical isotope labeling liquid chromatography mass spectrometry for exosome metabolomics","volume":"90","author":"Luo","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"126940","DOI":"10.1016\/j.talanta.2024.126940","article-title":"Metabolic landscaping of extracellular vesicles from body fluids by phosphatidylserine imprinted polymer enrichment and mass spectrometry analysis","volume":"282","author":"Lu","year":"2025","journal-title":"Talanta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s12964-021-00730-1","article-title":"The exosome journey: From biogenesis to uptake and intracellular signalling","volume":"19","author":"Gurung","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1016\/j.cmet.2021.08.006","article-title":"Exosomes as mediators of intercellular crosstalk in metabolism","volume":"33","author":"Isaac","year":"2021","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e70031","DOI":"10.1002\/mef2.70031","article-title":"Exosomes in metabolic diseases: From molecular mechanisms to clinical applications","volume":"4","author":"Wu","year":"2025","journal-title":"MedComm\u2013Future Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41392-020-00359-5","article-title":"Exosome-mediated metabolic reprogramming: The emerging role in tumor microenvironment remodeling and its influence on cancer progression","volume":"5","author":"Yang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"C832","DOI":"10.1152\/ajpcell.00053.2020","article-title":"Purinergic signaling, DAMPs, and inflammation","volume":"318","author":"Sarti","year":"2020","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1172\/JCI76369","article-title":"Emerging biology of sphingosine-1-phosphate: Its role in pathogenesis and therapy","volume":"125","author":"Proia","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e10250","DOI":"10.7554\/eLife.10250","article-title":"Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism","volume":"5","author":"Zhao","year":"2016","journal-title":"elife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1194\/jlr.M003657","article-title":"Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins","volume":"51","author":"Subra","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.scr.2013.01.002","article-title":"Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K\/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia\/reperfusion injury","volume":"10","author":"Arslan","year":"2013","journal-title":"Stem Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrclinonc.2016.60","article-title":"Cancer metabolism: A therapeutic perspective","volume":"14","author":"Pestell","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"27441","DOI":"10.1021\/acsami.7b06464","article-title":"Chemically edited exosomes with dual ligand purified by microfluidic device for active targeted drug delivery to tumor cells","volume":"9","author":"Wang","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.cmet.2017.03.008","article-title":"GPCR-mediated signaling of metabolites","volume":"25","author":"Husted","year":"2017","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.plipres.2017.03.001","article-title":"Lipids in exosomes: Current knowledge and the way forward","volume":"66","author":"Skotland","year":"2017","journal-title":"Prog. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1111\/tra.12803","article-title":"The role of lipids in exosome biology and intercellular communication: Function, analytics and applications","volume":"22","year":"2021","journal-title":"Traffic"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1194\/jlr.R084343","article-title":"Exosomal lipid composition and the role of ether lipids and phosphoinositides in exosome biology","volume":"60","author":"Skotland","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13046-020-01601-2","article-title":"Liquid biopsy and tumor heterogeneity in metastatic solid tumors: The potentiality of blood samples","volume":"39","author":"Russano","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40364-023-00507-3","article-title":"Cancer metabolites: Promising biomarkers for cancer liquid biopsy","volume":"11","author":"Wang","year":"2023","journal-title":"Biomark. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11585","DOI":"10.1038\/s41598-024-62360-0","article-title":"Identification of blood exosomal metabolomic profiling for high-altitude cerebral edema","volume":"14","author":"Tang","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s12967-023-04070-1","article-title":"Identification of serum exosomal metabolomic and proteomic profiles for remote ischemic preconditioning","volume":"21","author":"Du","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40001-023-01586-6","article-title":"Metabolomic profiling of exosomes reveals age-related changes in ovarian follicular fluid","volume":"29","author":"Gu","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/genetics\/130.1.231","article-title":"Multiple alleles and estimation of genetic parameters: Computational equations showing involvement of all alleles","volume":"130","author":"CHAKRABORTY","year":"1992","journal-title":"Genetics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Witwer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zebrowska, A., Skowronek, A., Wojakowska, A., Widlak, P., and Pietrowska, M. (2019). Metabolome of exosomes: Focus on vesicles released by cancer cells and present in human body fluids. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143461"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41392-024-01735-1","article-title":"Extracellular vesicles as tools and targets in therapy for diseases","volume":"9","author":"Kumar","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41556-018-0040-4","article-title":"Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation","volume":"20","author":"Zhang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12943-022-01671-0","article-title":"Exosome biogenesis: Machinery, regulation, and therapeutic implications in cancer","volume":"21","author":"Han","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.tcb.2023.06.006","article-title":"The ins-and-outs of exosome biogenesis, secretion, and internalization","volume":"34","author":"Arya","year":"2024","journal-title":"Trends Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.ymthe.2023.02.013","article-title":"Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading","volume":"31","author":"Gupta","year":"2023","journal-title":"Mol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1126\/science.aad8305","article-title":"Structure and membrane remodeling activity of ESCRT-III helical polymers","volume":"350","author":"McCullough","year":"2015","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.semcdb.2017.08.022","article-title":"Biogenesis and function of ESCRT-dependent extracellular vesicles","volume":"74","author":"Juan","year":"2018","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41422-020-00409-1","article-title":"RAB31 marks and controls an ESCRT-independent exosome pathway","volume":"31","author":"Wei","year":"2021","journal-title":"Cell Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1111\/j.1600-0854.2009.00920.x","article-title":"Multivesicular endosome biogenesis in the absence of ESCRTs","volume":"10","author":"Stuffers","year":"2009","journal-title":"Traffic"},{"key":"ref_46","first-page":"5553","article-title":"Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles","volume":"126","author":"Colombo","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"jcs259324","DOI":"10.1242\/jcs.259324","article-title":"Neutral sphingomyelinase 2 controls exosome secretion by counteracting V-ATPase-mediated endosome acidification","volume":"135","author":"Choezom","year":"2022","journal-title":"J. Cell Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1016\/j.drudis.2021.03.025","article-title":"Nipping disease in the bud: nSMase2 inhibitors as therapeutics in extracellular vesicle-mediated diseases","volume":"26","author":"Tallon","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1126\/science.1153124","article-title":"Ceramide triggers budding of exosome vesicles into multivesicular endosomes","volume":"319","author":"Trajkovic","year":"2008","journal-title":"Science"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/bs.acr.2018.05.004","article-title":"Ceramide and exosomes: A novel target in cancer biology and therapy","volume":"140","author":"Elsherbini","year":"2018","journal-title":"Adv. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12943-019-0963-9","article-title":"Mechanisms associated with biogenesis of exosomes in cancer","volume":"18","author":"McAndrews","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1038\/ncomms3712","article-title":"Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes","volume":"4","author":"Kajimoto","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yu, J., Sane, S., Kim, J.-E., Yun, S., Kim, H.-J., Jo, K.B., Wright, J.P., Khoshdoozmasouleh, N., Lee, K., and Oh, H.T. (2024). Biogenesis and delivery of extracellular vesicles: Harnessing the power of EVs for diagnostics and therapeutics. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1330400"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1111\/febs.12775","article-title":"Regulation of exosome release by glycosphingolipids and flotillins","volume":"281","author":"Phuyal","year":"2014","journal-title":"FEBS J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41594-024-01271-0","article-title":"Future opportunities in solute carrier structural biology","volume":"31","author":"Newstead","year":"2024","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.tibs.2023.05.011","article-title":"Targeting SLC transporters: Small molecules as modulators and therapeutic opportunities","volume":"48","author":"Schlessinger","year":"2023","journal-title":"Trends Biochem. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nrd4626","article-title":"SLC transporters as therapeutic targets: Emerging opportunities","volume":"14","author":"Lin","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s40364-024-00645-2","article-title":"The solute carrier transporters (SLCs) family in nutrient metabolism and ferroptosis","volume":"12","author":"Sun","year":"2024","journal-title":"Biomark. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1039\/C6MD00005C","article-title":"SLC transporters: Structure, function, and drug discovery","volume":"7","author":"Colas","year":"2016","journal-title":"Medchemcomm"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1038\/s41586-024-07062-3","article-title":"Ion and lipid orchestration of secondary active transport","volume":"626","author":"Drew","year":"2024","journal-title":"Nature"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Xie, S., Zhang, Q., and Jiang, L. (2022). Current knowledge on exosome biogenesis, cargo-sorting mechanism and therapeutic implications. Membranes, 12.","DOI":"10.3390\/membranes12050498"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Fang, Y., Wu, N., Gan, X., Yan, W., Morrell, J.C., and Gould, S.J. (2007). Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol., 5.","DOI":"10.1371\/journal.pbio.0050158"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1034\/j.1600-0854.2003.00072.x","article-title":"Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway","volume":"4","author":"Shimada","year":"2003","journal-title":"Traffic"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Li, Z., Yan, J., Li, X., Chen, H., Lin, C., Zhang, Y., Gao, T., Zhang, Y., Shu, Y., and Pan, S. (2025). Advancements in extracellular vesicles biomanufacturing: A comprehensive overview of large-scale production and clinical research. Front. Bioeng. Biotechnol., 13.","DOI":"10.3389\/fbioe.2025.1487627"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jmcb\/mjy052","article-title":"The SLC transporter in nutrient and metabolic sensing, regulation, and drug development","volume":"11","author":"Zhang","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gyimesi, G., and Hediger, M.A. (2022). Systematic in silico discovery of novel solute carrier-like proteins from proteomes. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271062"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"dmm050404","DOI":"10.1242\/dmm.050404","article-title":"Membrane transporters in cell physiology, cancer metabolism and drug response","volume":"16","author":"Alam","year":"2023","journal-title":"Dis. Models Mech."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Garcia, N.A., Ontoria-Oviedo, I., Gonz\u00e1lez-King, H., Diez-Juan, A., and Sep\u00falveda, P. (2015). Glucose starvation in cardiomyocytes enhances exosome secretion and promotes angiogenesis in endothelial cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138849"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/s12276-024-01209-y","article-title":"Regulation of cargo selection in exosome biogenesis and its biomedical applications in cancer","volume":"56","author":"Lee","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13046-023-02634-z","article-title":"Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment","volume":"42","author":"Tan","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s13238-018-0529-4","article-title":"Effect of pH, temperature and freezing-thawing on quantity changes and cellular uptake of exosomes","volume":"10","author":"Cheng","year":"2019","journal-title":"Protein Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s42003-019-0570-8","article-title":"Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping","volume":"2","author":"Rontogianni","year":"2019","journal-title":"Commun. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jmb.2015.09.019","article-title":"ExoCarta: A web-based compendium of exosomal cargo","volume":"428","author":"Keerthikumar","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.cca.2018.10.044","article-title":"Extracellular vesicles and energy metabolism","volume":"488","author":"Ronquist","year":"2019","journal-title":"Clin. Chim. Acta"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ymben.2017.01.001","article-title":"Exo-MFA\u2013a 13C metabolic flux analysis framework to dissect tumor microenvironment-secreted exosome contributions towards cancer cell metabolism","volume":"43","author":"Achreja","year":"2017","journal-title":"Metab. Eng."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.cell.2019.02.029","article-title":"Reassessment of exosome composition","volume":"177","author":"Jeppesen","year":"2019","journal-title":"Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"100273","DOI":"10.1016\/j.mcpro.2022.100273","article-title":"Quantitative proteomics identifies proteins enriched in large and small extracellular vesicles","volume":"21","author":"Lischnig","year":"2022","journal-title":"Mol. Cell. Proteom."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1007\/s10555-021-10014-2","article-title":"The role of the metabolite cargo of extracellular vesicles in tumor progression","volume":"40","author":"Harmati","year":"2021","journal-title":"Cancer Metastasis Rev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ncb2000","article-title":"Rab27a and Rab27b control different steps of the exosome secretion pathway","volume":"12","author":"Ostrowski","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1083\/jcb.200911018","article-title":"Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A\u2013C","volume":"189","author":"Hsu","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1080\/21541248.2016.1264352","article-title":"New insights into the function of Rab GTPases in the context of exosomal secretion","volume":"9","author":"Blanc","year":"2018","journal-title":"Small GTPases"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/s41467-019-09720-x","article-title":"KIBRA controls exosome secretion via inhibiting the proteasomal degradation of Rab27a","volume":"10","author":"Song","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Menaceur, C., Dusailly, O., Gosselet, F., Fenart, L., and Saint-Pol, J. (2023). Vesicular trafficking, a mechanism controlled by cascade activation of Rab proteins: Focus on Rab27. Biology, 12.","DOI":"10.3390\/biology12121530"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Komori, T., and Fukuda, M. (2024). Two roads diverged in a cell: Insights from differential exosome regulation in polarized cells. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1451988"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1242\/jcs.115.12.2505","article-title":"The exosome pathway in K562 cells is regulated by Rab11","volume":"115","author":"Savina","year":"2002","journal-title":"J. Cell Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.tcb.2011.08.007","article-title":"Endosomal transport via ubiquitination","volume":"21","author":"Piper","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"12356","DOI":"10.1002\/jev2.12356","article-title":"Identification of the SNARE complex that mediates the fusion of multivesicular bodies with the plasma membrane in exosome secretion","volume":"12","author":"Liu","year":"2023","journal-title":"J. Extracell. Vesicles"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e1600200","DOI":"10.1126\/sciadv.1600200","article-title":"Fundamentals of cancer metabolism","volume":"2","author":"DeBerardinis","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev-cancerbio-062822-120857","article-title":"Deciphering the Warburg effect: Metabolic reprogramming, epigenetic remodeling, and cell dedifferentiation","volume":"8","author":"Li","year":"2024","journal-title":"Annu. Rev. Cancer Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer cells","volume":"123","author":"Warburg","year":"1956","journal-title":"Science"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: How does it benefit cancer cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-019-0982-6","article-title":"Exosome-orchestrated hypoxic tumor microenvironment","volume":"18","author":"Meng","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3553617","DOI":"10.1155\/2022\/3553617","article-title":"Crosstalk between oxidative stress and exosomes","volume":"2022","author":"Zhang","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.cell.2012.01.021","article-title":"Hypoxia-inducible factors in physiology and medicine","volume":"148","author":"Semenza","year":"2012","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"14041","DOI":"10.1038\/ncomms14041","article-title":"Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23","volume":"8","author":"Wei","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.canlet.2018.08.001","article-title":"Exosomes derived from hypoxic epithelial ovarian cancer cells deliver microRNAs to macrophages and elicit a tumor-promoted phenotype","volume":"435","author":"Chen","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/s13402-019-00476-6","article-title":"Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic cancer cells enhance drug resistance by delivering miR-210","volume":"43","author":"Yang","year":"2020","journal-title":"Cell. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/aps.2017.178","article-title":"Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools","volume":"39","author":"Li","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.molmet.2019.07.006","article-title":"Monocarboxylate transporters in cancer","volume":"33","author":"Payen","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s10020-025-01205-6","article-title":"Warburg effect and lactylation in cancer: Mechanisms for chemoresistance","volume":"31","author":"Zhang","year":"2025","journal-title":"Mol. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1093\/bioinformatics\/btu741","article-title":"EVpedia: A community web portal for extracellular vesicles research","volume":"31","author":"Kim","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4389","DOI":"10.1038\/s41467-021-24384-2","article-title":"Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9","volume":"12","author":"Mathieu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"163","DOI":"10.7150\/ijbs.53671","article-title":"Regulation of exosome production and cargo sorting","volume":"17","author":"Wei","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1038\/ncomms3980","article-title":"Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs","volume":"4","author":"Mittelbrunn","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.canlet.2020.03.017","article-title":"Hypoxia in tumor microenvironment regulates exosome biogenesis: Molecular mechanisms and translational opportunities","volume":"479","author":"Kumar","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41580-023-00576-0","article-title":"Context-specific regulation of extracellular vesicle biogenesis and cargo selection","volume":"24","author":"Dixson","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_109","first-page":"1302","article-title":"Molecular lipidomics of exosomes released by PC-3 prostate cancer cells","volume":"1831","author":"Llorente","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1186\/s12951-023-02081-0","article-title":"Targeted therapy using engineered extracellular vesicles: Principles and strategies for membrane modification","volume":"21","author":"Liu","year":"2023","journal-title":"J. Nanobiotechnology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41565-024-01774-3","article-title":"Harnessing extracellular vesicle heterogeneity for diagnostic and therapeutic applications","volume":"20","author":"Carney","year":"2025","journal-title":"Nat. Nanotechnol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"113961","DOI":"10.1016\/j.addr.2021.113961","article-title":"Dosing extracellular vesicles","volume":"178","author":"Gupta","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"eadh1168","DOI":"10.1126\/sciadv.adh1168","article-title":"The cellular response to extracellular vesicles is dependent on their cell source and dose","volume":"9","author":"Hagey","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"14888","DOI":"10.1073\/pnas.1408301111","article-title":"Quantitative and stoichiometric analysis of the microRNA content of exosomes","volume":"111","author":"Chevillet","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"283","DOI":"10.20517\/evcna.2023.26","article-title":"Breaking free: Endocytosis and endosomal escape of extracellular vesicles","volume":"4","author":"Ribovski","year":"2023","journal-title":"Extracell. Vesicles Circ. Nucleic Acids"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"0148","DOI":"10.34133\/research.0148","article-title":"Advanced strategies for overcoming endosomal\/lysosomal barrier in nanodrug delivery","volume":"6","author":"Qiu","year":"2023","journal-title":"Research"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"106665","DOI":"10.1016\/j.phrs.2023.106665","article-title":"Endosomal escape of nucleic acids from extracellular vesicles mediates functional therapeutic delivery","volume":"188","author":"Pham","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41568-018-0037-0","article-title":"Extracellular ATP and P2 purinergic signalling in the tumour microenvironment","volume":"18","author":"Sarti","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Winzer, R., Nguyen, D.H., Schoppmeier, F., Cortesi, F., Gagliani, N., and Tolosa, E. (2024). Purinergic enzymes on extracellular vesicles: Immune modulation on the go. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1362996"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"115192","DOI":"10.1016\/j.bcp.2022.115192","article-title":"Interplay between purinergic signalling and extracellular vesicles in health and disease","volume":"203","author":"Carotti","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1083\/jcb.201703206","article-title":"Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling","volume":"217","author":"Verweij","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_122","first-page":"455","article-title":"Metabolic features of tumor-derived extracellular vesicles: Challenges and opportunities","volume":"5","author":"Sancho","year":"2024","journal-title":"Extracell. Vesicles Circ. Nucleic Acids"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Jacobson, K.A., Tosh, D.K., Jain, S., and Gao, Z.-G. (2019). Historical and current adenosine receptor agonists in preclinical and clinical development. Front. Cell. Neurosci., 13.","DOI":"10.3389\/fncel.2019.00124"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s42255-018-0014-7","article-title":"Coupling Krebs cycle metabolites to signalling in immunity and cancer","volume":"1","author":"Ryan","year":"2019","journal-title":"Nat. Metab."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Sagini, K., Costanzi, E., Emiliani, C., Buratta, S., and Urbanelli, L. (2018). Extracellular vesicles as conveyors of membrane-derived bioactive lipids in immune system. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041227"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.cell.2025.01.015","article-title":"Solute carriers: The gatekeepers of metabolism","volume":"188","author":"Khan","year":"2025","journal-title":"Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"120264","DOI":"10.1016\/j.biomaterials.2020.120264","article-title":"MSC-derived exosomes protect against oxidative stress-induced skin injury via adaptive regulation of the NRF2 defense system","volume":"257","author":"Wang","year":"2020","journal-title":"Biomaterials"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Chiaradia, E., Tancini, B., Emiliani, C., Delo, F., Pellegrino, R.M., Tognoloni, A., Urbanelli, L., and Buratta, S. (2021). Extracellular vesicles under oxidative stress conditions: Biological properties and physiological roles. Cells, 10.","DOI":"10.3390\/cells10071763"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cmet.2016.06.004","article-title":"Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation","volume":"24","author":"Lampropoulou","year":"2016","journal-title":"Cell Metab."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/nature25986","article-title":"Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1","volume":"556","author":"Mills","year":"2018","journal-title":"Nature"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/nature13085","article-title":"Nucleotide signalling during inflammation","volume":"509","author":"Idzko","year":"2014","journal-title":"Nature"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.jare.2024.03.027","article-title":"Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics","volume":"69","author":"Guo","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.bcp.2017.12.021","article-title":"The P2X7 receptor: A main player in inflammation","volume":"151","author":"Adinolfi","year":"2018","journal-title":"Biochem. Pharmacol."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Vultaggio-Poma, V., Sarti, A.C., and Di Virgilio, F. (2020). Extracellular ATP: A feasible target for cancer therapy. Cells, 9.","DOI":"10.3390\/cells9112496"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"100805","DOI":"10.1016\/j.bj.2024.100805","article-title":"Role of purinoreceptors in the release of extracellular vesicles and consequences on immune response and cancer progression","volume":"48","author":"Duret","year":"2025","journal-title":"Biomed. J."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Hu, Z., Matsuo, H., Du, S., Berzain Battioni, C., Jassowicz, L., Carretero, R., Sator-Schmitt, M., Zhao, X., Miao, B., and Eris, C. (2025). P2RY2 is a purinergic immune checkpoint linking extracellular ATP to immune evasion and adaptive resistance to immunotherapy. bioRxiv.","DOI":"10.1101\/2025.10.09.681049"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.molmed.2013.03.005","article-title":"CD39 and CD73 in immunity and inflammation","volume":"19","author":"Antonioli","year":"2013","journal-title":"Trends Mol. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1084\/jem.20062512","article-title":"Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression","volume":"204","author":"Deaglio","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"676","DOI":"10.4049\/jimmunol.1003884","article-title":"Cancer exosomes express CD39 and CD73, which suppress T cells through adenosine production","volume":"187","author":"Clayton","year":"2011","journal-title":"J. Immunol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"eaar5551","DOI":"10.1126\/science.aar5551","article-title":"Sphingosine 1-phosphate: Lipid signaling in pathology and therapy","volume":"366","author":"Cartier","year":"2019","journal-title":"Science"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/nrm1103","article-title":"Sphingosine-1-phosphate: An enigmatic signalling lipid","volume":"4","author":"Spiegel","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"e70687","DOI":"10.1002\/cam4.70687","article-title":"Exosomal lipids in cancer progression and metastasis","volume":"14","author":"Ramu","year":"2025","journal-title":"Cancer Med."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Mahajan-Thakur, S., Bien-M\u00f6ller, S., Marx, S., Schroeder, H., and Rauch, B.H. (2017). Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme\u2014A systematic review. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112448"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Duan, S., Nordmeier, S., Byrnes, A.E., and Buxton, I.L. (2021). Extracellular vesicle-mediated purinergic signaling contributes to host microenvironment plasticity and metastasis in triple negative breast cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020597"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12929-025-01186-y","article-title":"TCA cycle-derived oncometabolites in cancer and the immune microenvironment","volume":"32","author":"Sarkar","year":"2025","journal-title":"J. Biomed. Sci."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"0351","DOI":"10.34133\/research.0351","article-title":"The tricarboxylic acid cycle metabolites for cancer: Friend or enemy","volume":"7","author":"Wu","year":"2024","journal-title":"Research"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ccr.2012.02.014","article-title":"Metabolic reprogramming: A cancer hallmark even warburg did not anticipate","volume":"21","author":"Ward","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism","volume":"11","author":"Cairns","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ccr.2005.06.017","article-title":"HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: Novel role of fumarate in regulation of HIF stability","volume":"8","author":"Isaacs","year":"2005","journal-title":"Cancer Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"Kishton","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Viola, A., Munari, F., S\u00e1nchez-Rodr\u00edguez, R., Scolaro, T., and Castegna, A. (2019). The metabolic signature of macrophage responses. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01462"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Ji, Y., Li, X., Yao, X., Sun, J., Yi, J., Shen, Y., Chen, B., and Sun, H. (2025). Macrophage polarization: Molecular mechanisms, disease implications, and targeted therapeutic strategies. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1732718"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.it.2017.03.001","article-title":"Macrophage immunometabolism: Where are we (going)?","volume":"38","author":"Menon","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"15569","DOI":"10.2147\/IJN.S569204","article-title":"From Garden to Clinic: Plant-Derived Exosome-Like Nanovesicles for Precision Oxidative Stress Therapy","volume":"20","author":"Yang","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.immuni.2015.02.005","article-title":"Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization","volume":"42","author":"Jha","year":"2015","journal-title":"Immunity"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/s41419-025-08357-7","article-title":"Hypoxic tumor exosomes suppress macrophage inflammation and ferroptosis via NDUFV2 to enhance bystander tumor radioresistance","volume":"17","author":"Zhang","year":"2026","journal-title":"Cell Death Dis."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"5627","DOI":"10.1038\/s41467-023-41353-z","article-title":"Metabolic heterogeneity of tissue-resident macrophages in homeostasis and during helminth infection","volume":"14","author":"Heieis","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1038\/s41467-025-59878-w","article-title":"Dynamic single-cell metabolomics reveals cell-cell interaction between tumor cells and macrophages","volume":"16","author":"Zhang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e24454","DOI":"10.1016\/j.heliyon.2024.e24454","article-title":"Oncometabolite 2-hydroxyglutarate regulates anti-tumor immunity","volume":"10","author":"Cai","year":"2024","journal-title":"Heliyon"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s41577-019-0128-5","article-title":"Itaconate: The poster child of metabolic reprogramming in macrophage function","volume":"19","author":"Artyomov","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s41586-018-0052-z","article-title":"Electrophilic properties of itaconate and derivatives regulate the I\u03baB\u03b6\u2013ATF3 inflammatory axis","volume":"556","author":"Bambouskova","year":"2018","journal-title":"Nature"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tcb.2023.10.005","article-title":"Fumarate hydratase as a metabolic regulator of immunity","volume":"34","author":"Peace","year":"2024","journal-title":"Trends Cell Biol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.tibs.2024.05.003","article-title":"Functional implications of fumarate-induced cysteine succination","volume":"49","author":"Guberovic","year":"2024","journal-title":"Trends Biochem. Sci."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1101\/gad.191056.112","article-title":"Inhibition of \u03b1-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors","volume":"26","author":"Xiao","year":"2012","journal-title":"Genes Dev."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.it.2014.08.003","article-title":"Metabolic control of regulatory T cell development and function","volume":"36","author":"Zeng","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Mahamed, R., Monchusi, B., Penny, C., and Mirza, S. (2025). Cancer-derived exosomes: Mediators of immune crosstalk and emerging targets for immunotherapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1679934"},{"key":"ref_168","first-page":"257","article-title":"The Dual Role of Exosomes in the Tumor Microenvironment: From Pro-Tumorigenic Signaling to Immune Modulation","volume":"1","author":"Li","year":"2025","journal-title":"Med. Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s12276-023-01132-8","article-title":"Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: Current advances and therapeutic applications","volume":"56","author":"Jung","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"101147","DOI":"10.1016\/j.neo.2025.101147","article-title":"Exosomes in review: A new frontier in CAR-T cell therapies","volume":"62","author":"Wang","year":"2025","journal-title":"Neoplasia"},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Jiang, H., Zhao, H., Zhang, M., He, Y., Li, X., Xu, Y., and Liu, X. (2022). Hypoxia induced changes of exosome cargo and subsequent biological effects. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.824188"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Jin, H., Liu, J., and Wang, D. (2024). Antioxidant potential of exosomes in animal nutrition. Antioxidants, 13.","DOI":"10.3390\/antiox13080964"},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"King, H.W., Michael, M.Z., and Gleadle, J.M. (2012). Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer, 12.","DOI":"10.1186\/1471-2407-12-421"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"20083","DOI":"10.1074\/jbc.M301642200","article-title":"Exosome release is regulated by a calcium-dependent mechanism in K562 cells","volume":"278","author":"Savina","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1186\/s13287-017-0722-z","article-title":"MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction","volume":"8","author":"Chen","year":"2017","journal-title":"Stem Cell Res. Ther."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1186\/s13287-020-01756-x","article-title":"Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN\/AKT pathway","volume":"11","author":"Liu","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12964-023-01451-3","article-title":"Exosomes in skin photoaging: Biological functions and therapeutic opportunity","volume":"22","author":"Soheilifar","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Bao, X., Chen, L., Yu, H., Xie, Y., Luo, L., Luo, L., Wang, H., Chen, R., Cheng, Y., and Sun, D. (2025). Exosome-based modulation of ferroptosis in neurological disorders: Mechanisms, therapeutic potential, and translational challenges. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1677808"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1002\/stem.2618","article-title":"Hypoxia inducible factor-1\u03b1 potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes","volume":"35","author":"Ciria","year":"2017","journal-title":"Stem Cells"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.addr.2018.12.009","article-title":"Extracellular vesicles for personalized medicine: The input of physically triggered production, loading and theranostic properties","volume":"138","author":"Piffoux","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1080\/15476286.2015.1100795","article-title":"Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect","volume":"12","author":"Xu","year":"2015","journal-title":"RNA Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"7609","DOI":"10.1111\/jcmm.15397","article-title":"Extracellular vesicles enhance oxidative stress through P38\/NF-kB pathway in ketamine-induced ulcerative cystitis","volume":"24","author":"Xi","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Di Raimo, R., Mizzoni, D., Aloi, A., Pietrangelo, G., Dolo, V., Poppa, G., Fais, S., and Logozzi, M. (2024). Antioxidant effect of a plant-derived extracellular vesicles\u2019 mix on human skin fibroblasts: Induction of a reparative process. Antioxidants, 13.","DOI":"10.20944\/preprints202409.0288.v1"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1007\/s00432-025-06314-7","article-title":"Prediction models for different types of leukemia: A systematic review and critical appraisal","volume":"151","author":"Yang","year":"2025","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Wang, W., Zhen, S., Ping, Y., Wang, L., and Zhang, Y. (2024). Metabolomic biomarkers in liquid biopsy: Accurate cancer diagnosis and prognosis monitoring. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1331215"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1186\/s12935-024-03464-5","article-title":"Harnessing exosomes as cancer biomarkers in clinical oncology","volume":"24","author":"Ghosh","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.7150\/thno.52570","article-title":"Engineering exosomes for targeted drug delivery","volume":"11","author":"Liang","year":"2021","journal-title":"Theranostics"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1021\/acs.chemrev.7b00534","article-title":"New technologies for analysis of extracellular vesicles","volume":"118","author":"Shao","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/prca.201500083","article-title":"Integration of metabolomics and proteomics in multiple sclerosis: From biomarkers discovery to personalized medicine","volume":"10","author":"Rossi","year":"2016","journal-title":"Proteom.\u2013Clin. Appl."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"15593258251344480","DOI":"10.1177\/15593258251344480","article-title":"Exosome-Based Liquid Biopsy in Early Screening and Diagnosis of Cancers","volume":"23","author":"Hao","year":"2025","journal-title":"Dose-Response"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"102357","DOI":"10.1016\/j.arr.2024.102357","article-title":"Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance","volume":"99","author":"Gadhave","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"106816","DOI":"10.1016\/j.microc.2021.106816","article-title":"Recent technical advances to study metabolomics of extracellular vesicles","volume":"171","author":"Zhu","year":"2021","journal-title":"Microchem. J."},{"key":"ref_193","first-page":"120606","article-title":"Exosomal biomarkers in cancer: Insights from Multi-OMIC approaches","volume":"579","author":"Abuhelwa","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"14395","DOI":"10.1038\/s41598-017-14264-5","article-title":"A total transcriptome profiling method for plasma-derived extracellular vesicles: Applications for liquid biopsies","volume":"7","author":"Amorim","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"7164","DOI":"10.1038\/ncomms8164","article-title":"Directional cell movement through tissues is controlled by exosome secretion","volume":"6","author":"Sung","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"17679","DOI":"10.1021\/acs.analchem.4c03726","article-title":"Diagnosis and biomarker screening of endometrial cancer enabled by a versatile exosome metabolic fingerprint platform","volume":"96","author":"Yang","year":"2024","journal-title":"Anal. Chem."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12951-023-01908-0","article-title":"Metabolomic investigation of urinary extracellular vesicles for early detection and screening of lung cancer","volume":"21","author":"Yang","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1039\/C7NR08360B","article-title":"Technical challenges of working with extracellular vesicles","volume":"10","author":"Ramirez","year":"2018","journal-title":"Nanoscale"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13578-019-0282-2","article-title":"Exosomes: Biogenesis, biologic function and clinical potential","volume":"9","author":"Zhang","year":"2019","journal-title":"Cell Biosci."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12951-018-0403-9","article-title":"Recent advancements in the use of exosomes as drug delivery systems","volume":"16","author":"Bunggulawa","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s12929-024-01055-0","article-title":"Exosomes: A review of biologic function, diagnostic and targeted therapy applications, and clinical trials","volume":"31","author":"Chen","year":"2024","journal-title":"J. Biomed. Sci."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"237","DOI":"10.7150\/thno.21945","article-title":"Exosome theranostics: Biology and translational medicine","volume":"8","author":"He","year":"2018","journal-title":"Theranostics"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"17802","DOI":"10.1021\/acsnano.2c08774","article-title":"Exosomes\u2500 nature\u2019s lipid nanoparticles, a rising star in drug delivery and diagnostics","volume":"16","author":"Tenchov","year":"2022","journal-title":"ACS Nano"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41565-021-00931-2","article-title":"Extracellular vesicles as a next-generation drug delivery platform","volume":"16","author":"Herrmann","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref_205","doi-asserted-by":"crossref","unstructured":"Zhang, P., Chen, K., Liu, W., Niu, X., Wang, X., Wang, J., Yao, W., Tang, X., and Tian, W. (2025). Engineered exosomes: A promising design platform for overcoming cancer therapy resistance. Front. Cell Dev. Biol., 13.","DOI":"10.3389\/fcell.2025.1608480"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"736","DOI":"10.62347\/KIXF4662","article-title":"Application of engineered exosomes in tumor therapy","volume":"17","author":"Ma","year":"2025","journal-title":"Am. J. Transl. Res."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"eaat0195","DOI":"10.1126\/scitranslmed.aat0195","article-title":"Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy","volume":"10","author":"Gao","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"114978","DOI":"10.1016\/j.bios.2022.114978","article-title":"A novel peptide-templated AgNPs nanoprobe for theranostics of prostate cancer","volume":"223","author":"Cheng","year":"2023","journal-title":"Biosens. Bioelectron."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"100032","DOI":"10.1016\/j.vesic.2023.100032","article-title":"Exosome as drug delivery system: Current advancements","volume":"3","author":"Sharma","year":"2024","journal-title":"Extracell. Vesicle"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.1039\/D4NA00501E","article-title":"A comprehensive review of challenges and advances in exosome-based drug delivery systems","volume":"6","author":"Palakurthi","year":"2024","journal-title":"Nanoscale Adv."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.jconrel.2014.07.042","article-title":"Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit in vitro tumor growth: A new approach for drug delivery","volume":"192","author":"Pascucci","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Seow","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jconrel.2017.09.013","article-title":"Cancer-derived exosomes as a delivery platform of CRISPR\/Cas9 confer cancer cell tropism-dependent targeting","volume":"266","author":"Kim","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"155785","DOI":"10.1016\/j.prp.2024.155785","article-title":"Exosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing","volume":"266","author":"Balaraman","year":"2025","journal-title":"Pathol.-Res. Pract."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.7150\/thno.92703","article-title":"CRISPR-Cas9 library screening combined with an exosome-targeted delivery system addresses tumorigenesis\/TMZ resistance in the mesenchymal subtype of glioblastoma","volume":"14","author":"Zhao","year":"2024","journal-title":"Theranostics"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"1703244","DOI":"10.1080\/20013078.2019.1703244","article-title":"Inhibiting extracellular vesicles formation and release: A review of EV inhibitors","volume":"9","author":"Catalano","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"17442","DOI":"10.1074\/jbc.M110.107821","article-title":"Secretory mechanisms and intercellular transfer of microRNAs in living cells","volume":"285","author":"Kosaka","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"8161","DOI":"10.1038\/s41598-018-26411-7","article-title":"High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer","volume":"8","author":"Datta","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/imr.12528","article-title":"The ectonucleotidases CD 39 and CD 73: Novel checkpoint inhibitor targets","volume":"276","author":"Allard","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrc.2017.86","article-title":"Targeting immunosuppressive adenosine in cancer","volume":"17","author":"Vijayan","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"108700","DOI":"10.1016\/j.pharmthera.2024.108700","article-title":"Overview of the role of purinergic signaling and insights into its role in cancer therapy","volume":"262","author":"Tarantini","year":"2024","journal-title":"Pharmacol. Ther."},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Wang, Y., Li, Q., Zhou, S., and Tan, P. (2024). Contents of exosomes derived from adipose tissue and their regulation on inflammation, tumors, and diabetes. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1374715"},{"key":"ref_223","doi-asserted-by":"crossref","unstructured":"\u017bbikowski, A., B\u0142achnio-Zabielska, A., Galli, M., and Zabielski, P. (2021). Adipose-derived exosomes as possible players in the development of insulin resistance. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147427"},{"key":"ref_224","doi-asserted-by":"crossref","unstructured":"Xu, F., Xia, C., Dou, L., and Huang, X. (2023). Knowledge mapping of exosomes in metabolic diseases: A bibliometric analysis (2007-2022). Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1176430"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.jcmgh.2023.02.010","article-title":"Hepatic stellate cells: Dictating outcome in nonalcoholic fatty liver disease","volume":"15","author":"Wiering","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41575-021-00502-9","article-title":"Metabolomics and lipidomics in NAFLD: Biomarkers and non-invasive diagnostic tests","volume":"18","author":"Masoodi","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"e0310","DOI":"10.1097\/HC9.0000000000000310","article-title":"Gut microbiota and metabolic biomarkers in metabolic dysfunction\u2013associated steatotic liver disease","volume":"8","author":"Long","year":"2024","journal-title":"Hepatol. Commun."},{"key":"ref_228","doi-asserted-by":"crossref","unstructured":"Aoi, W., and Tanimura, Y. (2021). Roles of skeletal muscle-derived exosomes in organ metabolic and immunological communication. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.697204"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1016\/j.cmet.2023.10.013","article-title":"Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk","volume":"35","author":"Ma","year":"2023","journal-title":"Cell Metab."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1038\/s41596-020-00466-1","article-title":"Isolation and characterization of extracellular vesicle subpopulations from tissues","volume":"16","author":"Crescitelli","year":"2021","journal-title":"Nat. Protoc."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"24316","DOI":"10.1038\/srep24316","article-title":"Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection","volume":"6","author":"Kittel","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"44386","DOI":"10.1021\/acsami.4c03869","article-title":"Improving the purity of extracellular vesicles by removal of lipoproteins from size exclusion chromatography-and ultracentrifugation-processed samples using glycosaminoglycan-functionalized magnetic beads","volume":"16","author":"Chou","year":"2024","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"e70047","DOI":"10.1002\/jex2.70047","article-title":"Development of an effective isolation method for plasma extracellular vesicles excluding lipoproteins by precipitation with polyethylene glycol","volume":"4","author":"Otani","year":"2025","journal-title":"J. Extracell. Biol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1038\/s41596-023-00811-0","article-title":"Comprehensive isolation of extracellular vesicles and nanoparticles","volume":"18","author":"Zhang","year":"2023","journal-title":"Nat. Protoc."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"2103222","DOI":"10.1002\/advs.202103222","article-title":"Exosome processing and characterization approaches for research and technology development","volume":"9","author":"Lai","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"342473","DOI":"10.1016\/j.aca.2024.342473","article-title":"A comprehensive guide to extract information from extracellular vesicles: A tutorial review towards novel analytical developments","volume":"1302","author":"Romano","year":"2024","journal-title":"Anal. Chim. Acta"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"e12416","DOI":"10.1002\/jev2.12416","article-title":"MISEV2023: An updated guide to EV research and applications","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"e70099","DOI":"10.1002\/jssc.70099","article-title":"From complexity to clarity: Expanding metabolome coverage with innovative analytical strategies","volume":"48","author":"Aarika","year":"2025","journal-title":"J. Sep. Sci."},{"key":"ref_239","first-page":"1","article-title":"Metabolomics: A review of liquid chromatography mass spectrometry-based methods and clinical applications","volume":"49","year":"2024","journal-title":"Turk. J. Biochem."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"e2400007","DOI":"10.1002\/ansa.202400007","article-title":"Challenges and recent advances in quantitative mass spectrometry-based metabolomics","volume":"5","author":"Ghafari","year":"2024","journal-title":"Anal. Sci. Adv."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s43556-025-00345-9","article-title":"CD39 and CD73: Biological functions, diseases and therapy","volume":"6","author":"Shen","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Kleuser, B., and B\u00e4umer, W. (2023). Sphingosine 1-phosphate as essential signaling molecule in inflammatory skin diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021456"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/ars.2017.7216","article-title":"NAD (H) and NADP (H) redox couples and cellular energy metabolism","volume":"28","author":"Xiao","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1093\/stcltm\/szae052","article-title":"MISEV2023 provides an updated and key reference for researchers studying the basic biology and applications of extracellular vesicles","volume":"13","author":"Upadhya","year":"2024","journal-title":"Stem Cells Transl. Med."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/3\/207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T11:07:48Z","timestamp":1774004868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/3\/207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,20]]},"references-count":244,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["metabo16030207"],"URL":"https:\/\/doi.org\/10.3390\/metabo16030207","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,20]]}}}