{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:21:21Z","timestamp":1780460481085,"version":"3.54.1"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002468","name":"Dong-A University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002468","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>Cytokine release syndrome (CRS) is a systemic inflammatory response resulting in overexpression of cytokines in serum and tissues, which leads to multiple-organ failure. Due to rapid aggravation of symptoms, timely intervention is paramount; however, current therapies are limited in their capacity to address CRS. Here, we find that the intravenous injection of highly purified detonation-synthesized nanodiamonds (DND) can act as a therapeutic agent for treating CRS by adsorbing inflammatory cytokines. Highly purified DNDs successfully inactivated various key cytokines in plasma from CRS patients with pneumonia, septic shock, and coronavirus disease 2019 pandemic (COVID-19). The intravenous injection of the DND samples in a mouse sepsis model by cecal ligation and puncture significantly improved survival rates and prevented tissue damage by reducing the circulating inflammatory cytokines. The results of this study suggest that the clinical application of highly purified DND can provide survival benefits for CRS patients by adsorbing inflammatory cytokines.<\/jats:p>","DOI":"10.3389\/fbioe.2022.862495","type":"journal-article","created":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T09:04:39Z","timestamp":1649063079000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Nanodiamond as a Cytokine Sponge in Infectious Diseases"],"prefix":"10.3389","volume":"10","author":[{"given":"Wonbeak","family":"Yoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonhwa","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Nam","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyoung","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Ho","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June Hong","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juheon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-su","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Whan","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Seob","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seokho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.jinf.2004.09.008","article-title":"The Use of Corticosteroid as Treatment in SARS Was Associated with Adverse Outcomes: a Retrospective Cohort Study","volume":"51","author":"Auyeung","year":"2005","journal-title":"J. Infect."},{"key":"B2","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.nano.2015.11.011","article-title":"Biological Interactions of Carbon-Based Nanomaterials: From Coronation to Degradation","volume":"12","author":"Bhattacharya","year":"2016","journal-title":"Nanomedicine: Nanotechnology, Biol. Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"342","DOI":"10.15386\/mpr-1756","article-title":"A Review of the Current Understanding of Nanoparticles Protein corona Composition","volume":"93","author":"Breznica","year":"2020","journal-title":"Med. Pharm. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/0261-5614(92)90006-c","article-title":"Particle Size, Surface Hydrophobicity and Interaction with Serum of Parenteral Fat Emulsions and Model Drug Carriers as Parameters Related to RES Uptake","volume":"11","author":"Carrstensen","year":"1992","journal-title":"Clin. Nutr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"5754","DOI":"10.1002\/anie.200700465","article-title":"Detailed Identification of Plasma Proteins Adsorbed on Copolymer Nanoparticles","volume":"46","author":"Cedervall","year":"2007","journal-title":"Angew. Chem. Int. Ed."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jpha.2019.09.003","article-title":"Nanodiamonds with Powerful Ability for Drug Delivery and Biomedical Applications: Recent Updates on In Vivo Study and Patents","volume":"10","author":"Chauhan","year":"2020","journal-title":"J. Pharm. Anal."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1378\/chest.129.6.1441","article-title":"Treatment of Severe Acute Respiratory Syndrome with Glucosteroids","volume":"129","author":"Chen","year":"2006","journal-title":"Chest"},{"key":"B8","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00281-017-0639-8","article-title":"Cytokine Storm and Sepsis Disease Pathogenesis","volume":"39","author":"Chousterman","year":"2017","journal-title":"Semin. Immunopathol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1038\/s41419-018-0280-z","article-title":"Non-toxic Engineered Carbon Nanodiamond Concentrations Induce Oxidative\/nitrosative Stress, Imbalance of Energy Metabolism, and Mitochondrial Dysfunction in Microglial and Alveolar Basal Epithelial Cells","volume":"9","author":"Fresta","year":"2018","journal-title":"Cell Death Dis"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1002\/lt.24005","article-title":"First Description of Single-Pass Albumin Dialysis Combined with Cytokine Adsorption in Fulminant Liver Failure and Hemophagocytic Syndrome Resulting from Generalized Herpes Simplex Virus 1 Infection","volume":"20","author":"Frimmel","year":"2014","journal-title":"Liver Transpl."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1902238","DOI":"10.1002\/smll.201902238","article-title":"Nanodiamond\u2010Based Theranostic Platform for Drug Delivery and Bioimaging","volume":"15","author":"Gao","year":"2019","journal-title":"Small"},{"key":"B12","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1002\/jbm.a.10371","article-title":"Functional Groups on Polystyrene Model Nanoparticles: Influence on Protein Adsorption","author":"Gessner","year":"2003","journal-title":"J. Biomed. Mater. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/s41591-018-0041-7","article-title":"CAR T Cell-Induced Cytokine Release Syndrome Is Mediated by Macrophages and Abated by IL-1 Blockade","volume":"24","author":"Giavridis","year":"2018","journal-title":"Nat. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s10875-017-0377-7","article-title":"Rescue of Cytokine Storm Due to HLH by Hemoadsorption in a CTLA4-Deficient Patient","volume":"37","author":"Greil","year":"2017","journal-title":"J. Clin. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.diamond.2017.11.006","article-title":"Atmospheric-pressure Chemical Purification of Detonation-Synthesized Nanodiamond by Using Perchloric Acid: Intensive Parametric Study to Control Sp3\/sp2carbon Ratio","volume":"81","author":"Hong","year":"2018","journal-title":"Diamond Relat. Mater."},{"key":"B16","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1186\/cc1826","article-title":"Hemofiltration, Adsorption, Sieving and the challenge of Sepsis Therapy Design","volume":"6","author":"Honor\u00e9","year":"2002","journal-title":"Crit. Care"},{"key":"B17","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1186\/s12951-020-00704-4","article-title":"Role of Capping Agents in the Application of Nanoparticles in Biomedicine and Environmental Remediation: Recent Trends and Future Prospects","volume":"18","author":"Javed","year":"2020","journal-title":"J. Nanobiotechnol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2006110","DOI":"10.1002\/adfm.202006110","article-title":"Ferritin Nanocage\u2010Based Methyltransferase SETD6 for COVID\u201019 Therapy","volume":"30","author":"Kim","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"B19","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.jconrel.2014.06.046","article-title":"PEG - a Versatile Conjugating Ligand for Drugs and Drug Delivery Systems","volume":"192","author":"Kolate","year":"2014","journal-title":"J. Controlled Release"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1080\/17435390.2020.1813825","article-title":"The Sp3\/sp2 Carbon Ratio as a Modulator of In Vivo and In Vitro Toxicity of the Chemically Purified Detonation-Synthesized Nanodiamond via the Reactive Oxygen Species Generation","volume":"14","author":"Lee","year":"","journal-title":"Nanotoxicology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current Concepts in the Diagnosis and Management of Cytokine Release Syndrome","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"B22","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"B23","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41392-020-00292-7","article-title":"COVID-19-activated SREBP2 Disturbs Cholesterol Biosynthesis and Leads to Cytokine Storm","volume":"5","author":"Lee","year":"","journal-title":"Sig Transduct Target. Ther."},{"key":"B24","doi-asserted-by":"publisher","first-page":"7334","DOI":"10.1021\/nn202190c","article-title":"Origin of Enhanced Stem Cell Growth and Differentiation on Graphene and Graphene Oxide","volume":"5","author":"Lee","year":"2011","journal-title":"ACS Nano"},{"key":"B25","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1080\/15287394.2014.955158","article-title":"Determination of Adsorption Affinity of Nanoparticles for Interleukin-8 Secreted from A549 Cells by In Vitro Cell-free and Cell-Based Assays","volume":"78","author":"Lee","year":"2015","journal-title":"J. Toxicol. Environ. Health A"},{"key":"B26","doi-asserted-by":"publisher","first-page":"108408","DOI":"10.1016\/j.clim.2020.108408","article-title":"Potential Effect of Blood Purification Therapy in Reducing Cytokine Storm as a Late Complication of Critically Ill COVID-19","volume":"214","author":"Ma","year":"2020","journal-title":"Clin. Immunol."},{"key":"B27","first-page":"209","article-title":"Blood Filtration: New Opportunities and the Implications of Systems Biology","volume":"6","author":"Matson","year":"2004","journal-title":"Crit. Care Resusc"},{"key":"B28","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1186\/s13054-016-1570-4","article-title":"The Inflammatory Response to Extracorporeal Membrane Oxygenation (ECMO): a Review of the Pathophysiology","volume":"20","author":"Millar","year":"2016","journal-title":"Crit. Care"},{"key":"B29","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nnano.2011.209","article-title":"The Properties and Applications of Nanodiamonds","volume":"7","author":"Mochalin","year":"2011","journal-title":"Nat. Nanotech"},{"key":"B30","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nmat2442","article-title":"Understanding Biophysicochemical Interactions at the Nano-Bio Interface","volume":"8","author":"Nel","year":"2009","journal-title":"Nat. Mater"},{"key":"B31","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/s41591-018-0036-4","article-title":"Monocyte-derived IL-1 and IL-6 Are Differentially Required for Cytokine-Release Syndrome and Neurotoxicity Due to CAR T Cells","volume":"24","author":"Norelli","year":"2018","journal-title":"Nat. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"eabc1564","DOI":"10.1126\/sciadv.abc1564","article-title":"Acetylated K676 TGFBIp as a Severity Diagnostic Blood Biomarker for SARS-CoV-2 Pneumonia","volume":"6","author":"Park","year":"2020","journal-title":"Sci. Adv."},{"key":"B33","doi-asserted-by":"publisher","first-page":"14914","DOI":"10.1038\/s41598-017-15116-y","article-title":"Carbon Adsorbents with Dual Porosity for Efficient Removal of Uremic Toxins and Cytokines from Human Plasma","volume":"7","author":"Pavlenko","year":"2017","journal-title":"Sci. Rep."},{"key":"B34","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/nprot.2008.214","article-title":"Immunodesign of Experimental Sepsis by Cecal Ligation and Puncture","volume":"4","author":"Rittirsch","year":"2009","journal-title":"Nat. Protoc."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e0187015","DOI":"10.1371\/journal.pone.0187015","article-title":"The Effect of a Novel Extracorporeal Cytokine Hemoadsorption Device on IL-6 Elimination in Septic Patients: A Randomized Controlled Trial","volume":"12","author":"Sch\u00e4dler","year":"2017","journal-title":"PLoS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"P62","DOI":"10.1186\/cc12000","article-title":"A Multicenter Randomized Controlled Study of an Extracorporeal Cytokine Hemoadsorption Device in Septic Patients","volume":"17","author":"Sch\u00e4dler","year":"2013","journal-title":"Crit. Care"},{"key":"B37","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1111\/j.1365-2567.2006.02435.x","article-title":"Polymorphonuclear Leucocytes Selectively Produce Anti-inflammatory Interleukin-1 Receptor Antagonist and Chemokines, but Fail to Produce Pro-inflammatory Mediators","volume":"119","author":"Schr\u00f6der","year":"2006","journal-title":"Immunology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12929-017-0370-8","article-title":"Comprehensive Comparison of Three Different Animal Models for Systemic Inflammation","volume":"24","author":"Seemann","year":"2017","journal-title":"J. Biomed. Sci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1021\/acsabm.8b00151","article-title":"Graphene-Based Materials for the Fast Removal of Cytokines from Blood Plasma","volume":"1","author":"Seredych","year":"2018","journal-title":"ACS Appl. Bio Mater."},{"key":"B40","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1097\/CCM.0000000000001402","article-title":"Interleukin-1 Receptor Blockade Is Associated with Reduced Mortality in Sepsis Patients with Features of Macrophage Activation Syndrome","volume":"44","author":"Shakoory","year":"2016","journal-title":"Crit. Care Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine Release Syndrome","volume":"6","author":"Shimabukuro-Vornhagen","year":"2018","journal-title":"J. Immunotherapy Cancer"},{"key":"B42","doi-asserted-by":"publisher","first-page":"102162","DOI":"10.1016\/j.cis.2020.102162","article-title":"Nanoparticle Processing: Understanding and Controlling Aggregation","volume":"279","author":"Shrestha","year":"2020","journal-title":"Adv. Colloid Interf. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B44","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1182\/blood-2018-10-881722","article-title":"GM-CSF Inhibition Reduces Cytokine Release Syndrome and Neuroinflammation but Enhances CAR-T Cell Function in Xenografts","volume":"133","author":"Sterner","year":"2019","journal-title":"Blood"},{"key":"B45","doi-asserted-by":"publisher","first-page":"959","DOI":"10.2217\/imt-2016-0020","article-title":"Immunotherapeutic Implications of IL-6 Blockade for Cytokine Storm","volume":"8","author":"Tanaka","year":"2016","journal-title":"Immunotherapy"},{"key":"B46","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1021\/nn405019v","article-title":"Impact of Protein Modification on the Protein corona on Nanoparticles and Nanoparticle-Cell Interactions","volume":"8","author":"Treuel","year":"2014","journal-title":"ACS Nano"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.3390\/ijms17071111","article-title":"Nanodiamonds for Medical Applications: Interaction with Blood In Vitro and In Vivo","volume":"17","author":"Tsai","year":"2016","journal-title":"Ijms"},{"key":"B48","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nri.2017.36","article-title":"The Immunopathology of Sepsis and Potential Therapeutic Targets","volume":"17","author":"van der Poll","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1093\/cvr\/cvu062","article-title":"Crosstalk between Fibroblasts and Inflammatory Cells","volume":"102","author":"Van Linthout","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1158\/1078-0432.CCR-18-1379","article-title":"Plasma Exchange Can Be an Alternative Therapeutic Modality for Severe Cytokine Release Syndrome after Chimeric Antigen Receptor-T Cell Infusion: A Case Report","volume":"25","author":"Xiao","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"4789","DOI":"10.1016\/j.biomaterials.2010.02.054","article-title":"Mesoporous Carbide-Derived Carbon for Cytokine Removal from Blood Plasma","volume":"31","author":"Yachamaneni","year":"2010","journal-title":"Biomaterials"},{"key":"B52","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s41392-020-00243-2","article-title":"COVID-19: Immunopathogenesis and Immunotherapeutics","volume":"5","author":"Yang","year":"2020","journal-title":"Sig Transduct Target. Ther."},{"key":"B53","doi-asserted-by":"publisher","first-page":"210","DOI":"10.3389\/fbioe.2020.00210","article-title":"Regulating Protein Corona Formation and Dynamic Protein Exchange by Controlling Nanoparticle Hydrophobicity","volume":"8","author":"Yu","year":"2020","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"5755","DOI":"10.1016\/j.biomaterials.2006.07.019","article-title":"Mesoporous Carbide-Derived Carbon with Porosity Tuned for Efficient Adsorption of Cytokines","volume":"27","author":"Yushin","year":"2006","journal-title":"Biomaterials"},{"key":"B55","doi-asserted-by":"publisher","first-page":"302","DOI":"10.7150\/thno.3627","article-title":"The Biocompatibility of Nanodiamonds and Their Application in Drug Delivery Systems","volume":"2","author":"Zhu","year":"2012","journal-title":"Theranostics"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2022.862495\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T09:04:43Z","timestamp":1649063083000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2022.862495\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,4]]},"references-count":55,"alternative-id":["10.3389\/fbioe.2022.862495"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2022.862495","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,4]]},"article-number":"862495"}}