{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:23:16Z","timestamp":1781601796639,"version":"3.54.5"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T00:00:00Z","timestamp":1605830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention &amp; Research Institute of Texas","doi-asserted-by":"publisher","award":["RP170466"],"award-info":[{"award-number":["RP170466"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000883","name":"Brown Foundation","doi-asserted-by":"publisher","award":["18130011"],"award-info":[{"award-number":["18130011"]}],"id":[{"id":"10.13039\/100000883","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Regenerative Medicine Program Cullen Trust for Health Care","award":["18130014"],"award-info":[{"award-number":["18130014"]}]},{"name":"Hearst Foundation","award":["18130017"],"award-info":[{"award-number":["18130017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Recent studies on coronavirus infectious disease 2019 (COVID-19) pathophysiology indicated the cytokine release syndrome induced by the virus as the main cause of mortality. Patients with severe COVID-19 infection present a systemic hyper inflammation that can lead to lung and multi-organ injuries. Among the most recent treatments, corticosteroids have been identified to be effective in mitigating these catastrophic effects. Our group has recently developed leukocyte-derived nanovesicles, termed leukosomes, able to target in vivo the inflamed vasculature associated with pathological conditions including cancer, cardiovascular diseases, and sepsis. Herein, to gain insights on the anti-inflammatory properties of leukosomes, we investigated their ability to reduce uncontrolled inflammation in a lethal model of lipopolysaccharide (LPS)-induced endotoxemia, recapitulating the cytokine storm syndrome observed in COVID-19 infection after encapsulating dexamethasone. Treated animals showed a significant survival advantage and an improved immune response resolution, as demonstrated by a cytokine array analysis of pro- and anti-inflammatory cytokines, chemokines, and other immune-relevant markers. Our results showed that leukosomes enhance the therapeutic activity of dexamethasone and better control the inflammatory response compared to the free drug. Such an approach could be useful for the development of personalized therapies in the treatment of hyperinflammation related to infectious diseases, including the ones caused by COVID-19.<\/jats:p>","DOI":"10.3390\/nano10112301","type":"journal-article","created":{"date-parts":[[2020,11,20]],"date-time":"2020-11-20T09:46:18Z","timestamp":1605865578000},"page":"2301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Biomimetic Nanoparticles Potentiate the Anti-Inflammatory Properties of Dexamethasone and Reduce the Cytokine Storm Syndrome: An Additional Weapon against COVID-19?"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8030-0892","authenticated-orcid":false,"given":"Roberto","family":"Molinaro","sequence":"first","affiliation":[{"name":"Center for Biomimetic Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"IRCCS San Raffaele Hospital, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pasto","sequence":"additional","affiliation":[{"name":"Center for Biomimetic Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4959-1169","authenticated-orcid":false,"given":"Francesca","family":"Taraballi","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Regeneration, Houston Methodist Academic Institute, Houston, TX 77030, USA"},{"name":"Orthopedics and Sport Medicine, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Giordano","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Regeneration, Houston Methodist Academic Institute, Houston, TX 77030, USA"},{"name":"Orthopedics and Sport Medicine, Houston Methodist Hospital, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamil A.","family":"Azzi","sequence":"additional","affiliation":[{"name":"Renal Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ennio","family":"Tasciotti","sequence":"additional","affiliation":[{"name":"Center for Biomimetic Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Orthopedics and Sport Medicine, Houston Methodist Hospital, Houston, TX 77030, USA"},{"name":"Biotechnology Program, San Raffaele University and IRCCS San Raffaele Pisana, 00166 Roma RM, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6468-2571","authenticated-orcid":false,"given":"Claudia","family":"Corbo","sequence":"additional","affiliation":[{"name":"Center for Biomimetic Medicine, Houston Methodist Research Institute, Houston, TX 77030, USA"},{"name":"Department of Medicine and Surgery, Center for Nanomedicine Nanomib, University of Milan Bicocca, 20854 Vedano al Lambro MB, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Horby, P., Lim, W.S., Emberson, J.R., Mafham, M., Bell, J.L., Linsell, L., Staplin, N., Brightling, C., Ustianowski, A., and Elmahi, E. (2020). Dexamethasone in Hospitalized Patients with Covid-19\u2014Preliminary Report. N. Engl. J. Med.","DOI":"10.1101\/2020.06.22.20137273"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41577-020-00421-x","article-title":"After 62 years of regulating immunity, dexamethasone meets COVID-19","volume":"20","author":"Cain","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.2217\/nnm.15.39","article-title":"Enabling cytoplasmic delivery and organelle targeting by surface modification of nanocarriers","volume":"10","author":"Parodi","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.biomaterials.2017.09.020","article-title":"Bio-inspired engineering of cell- and virus-like nanoparticles for drug delivery","volume":"147","author":"Parodi","year":"2017","journal-title":"Biomaterials"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.2174\/0929867325666180831150259","article-title":"Exosome-like nanovectors for drug delivery in cancer","volume":"26","author":"Arrighetti","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34422","DOI":"10.1038\/srep34422","article-title":"Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability","volume":"6","author":"Palomba","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.2174\/1389450115666141109211413","article-title":"Proteomic Profiling of a Biomimetic Drug Delivery Platform","volume":"16","author":"Corbo","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1038\/s41467-018-03915-4","article-title":"A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nnano.2013.54","article-title":"A biomimetic nanosponge that absorbs pore-forming toxins","volume":"8","author":"Hu","year":"2013","journal-title":"Nat. Nanotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1021\/acs.nanolett.7b05263","article-title":"Macrophage-Membrane-Coated Nanoparticles for Tumor-Targeted Chemotherapy","volume":"18","author":"Zhang","year":"2018","journal-title":"Nano Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/nmat4644","article-title":"Biomimetic proteolipid vesicles for targeting inflamed tissues","volume":"15","author":"Molinaro","year":"2016","journal-title":"Nat. Mater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.7150\/thno.22078","article-title":"Biomimetic nanoparticles with enhanced affinity towards activated endothelium as versatile tools for theranostic drug delivery","volume":"8","author":"Martinez","year":"2018","journal-title":"Theranostics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11488","DOI":"10.1073\/pnas.1714267114","article-title":"Macrophage-like nanoparticles concurrently absorbing endotoxins and proinflammatory cytokines for sepsis management","volume":"114","author":"Thamphiwatana","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.biomaterials.2018.10.029","article-title":"Engineered nanoparticles disguised as macrophages for trapping lipopolysaccharide and preventing endotoxemia","volume":"189","author":"Shen","year":"2019","journal-title":"Biomaterials"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1021\/acsnano.7b00376","article-title":"Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers","volume":"11","author":"Corbo","year":"2017","journal-title":"ACS Nano"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1902333","DOI":"10.1002\/smll.201902333","article-title":"Biohybrid Nanoparticles to Negotiate with Biological Barriers","volume":"15","author":"Mohammadi","year":"2019","journal-title":"Small"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1161\/CIRCRESAHA.119.315185","article-title":"Rapamycin-Loaded Biomimetic Nanoparticles Reverse Vascular Inflammation","volume":"126","author":"Boada","year":"2020","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1039\/C9BM01766F","article-title":"Leukocyte-mimicking nanovesicles for effective doxorubicin delivery to treat breast cancer and melanoma","volume":"8","author":"Molinaro","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.2174\/0929867324666170920160030","article-title":"Inflammation and Cancer: In Medio Stat Nano","volume":"25","author":"Molinaro","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13576","DOI":"10.1039\/C9NR04253A","article-title":"Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages","volume":"11","author":"Molinaro","year":"2019","journal-title":"Nanoscale"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14581","DOI":"10.1039\/C7NR04734G","article-title":"Engineered biomimetic nanovesicles show intrinsic anti-inflammatory properties for the treatment of inflammatory bowel diseases","volume":"9","author":"Corbo","year":"2017","journal-title":"Nanoscale"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1702749","DOI":"10.1002\/adma.201702749","article-title":"Design and Development of Biomimetic Nanovesicles Using a Microfluidic Approach","volume":"30","author":"Molinaro","year":"2018","journal-title":"Adv. Mater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1056\/NEJMcibr1007320","article-title":"Sepsis and endothelial permeability","volume":"363","author":"Lee","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wilson, J.G., Simpson, L.J., Ferreira, A.M., Rustagi, A., Roque, J., Asuni, A., Ranganath, T., Grant, P.M., Subramanian, A., and Rosenberg-Hasson, Y. (2020). Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI Insight, e140289.","DOI":"10.1101\/2020.05.15.20103549"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cytogfr.2020.05.003","article-title":"The cytokine storm in COVID-19: An overview of the involvement of the chemokine\/chemokine-receptor system","volume":"53","author":"Coperchini","year":"2020","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.4049\/jimmunol.1900790","article-title":"TNF-\u03b1 and IL-10 Control CXCL13 Expression in Human Macrophages","volume":"204","author":"Bellamri","year":"2020","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Carvelli, J., Demaria, O., V\u00e9ly, F., Batista, L., Benmansour, N.C., Fares, J., Carpentier, S., Thibult, M.-L., Morel, A., and Remark, R. (2020). Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis. Nature.","DOI":"10.1136\/jitc-2020-SITC2020.0483"}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/10\/11\/2301\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:35:05Z","timestamp":1760178905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/10\/11\/2301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,20]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["nano10112301"],"URL":"https:\/\/doi.org\/10.3390\/nano10112301","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,20]]}}}