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Although re\u2010instatement of immune balance does alleviate MS symptoms, exploration of concomitant complement inhibition for neuron protection has not been evaluated. Herein, we developed myelin oligodendrocyte glycoprotein 35\u201055 (MOG) peptide and artemisinin (ART) co\u2010loaded liposomes (MOG\u2010ART\u2010Lip) to simultaneously restore immune balance and inhibit complement activation. This nanoplatform enhanced solubility of both components while enabling CNS delivery. Liposomes loaded with MOG would induce tolerogenic DCs (tol\u2010DCs) that express low\u2010levels of costimulatory molecules, capable of antigenic peptide presentation and induction of regulatory T cells, while ART shifted microglia from pro\u2010inflammatory (M1) to anti\u2010inflammatory (M2) phenotypes. Importantly, ART suppressed complement\u2010mediated demyelination via the C3\/C3a receptor (C3aR) pathway. In vivo studies showed MOG\u2010ART\u2010Lip significantly reduced neuroinflammation, attenuated demyelination, and promoted neural repair, leading to functional recovery. Overall, results of this study suggest that a combination of an auto\u2010antigenic peptide and an immune\u2010modulator provides a promising modality for the treatment of MS by re\u2010establishing antigen\u2010specific immune tolerance. As such, the results of the study provide valuable insight into a new approach for development of combinatorial complement therapies for the treatment of MS patients.<\/jats:p>","DOI":"10.1002\/adhm.202403774","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T06:35:24Z","timestamp":1752820524000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunological Tolerance Induced by Nanoliposome with Autoantigenie Peptide and Artesunate to Inhibit Complement and Remodel Immune Balance for Multiple Sclerosis Treatment"],"prefix":"10.1002","volume":"14","author":[{"given":"Yaya","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Preparation General Hospital of Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanlan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbao","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-3257","authenticated-orcid":false,"given":"Jianhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_1_1","DOI":"10.1016\/S0140-6736(18)30481-1"},{"doi-asserted-by":"publisher","key":"e_1_2_10_2_1","DOI":"10.1111\/ene.13819"},{"key":"e_1_2_10_3_1","first-page":"1","volume":"19","author":"Ghasemi N.","year":"2017","journal-title":"Cell J."},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_1","DOI":"10.1172\/JCI160468"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_1","DOI":"10.1056\/NEJMra1401483"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_1","DOI":"10.1007\/s00011-018-1185-0"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_1","DOI":"10.3389\/fphar.2021.724718"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_1","DOI":"10.1016\/B978-0-444-52001-2.00022-4"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_1","DOI":"10.1002\/ana.24398"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_1","DOI":"10.1186\/s12974-016-0611-x"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_1","DOI":"10.1093\/brain\/awx154"},{"doi-asserted-by":"publisher","key":"e_1_2_10_12_1","DOI":"10.1056\/NEJMcibr2032177"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_1","DOI":"10.1038\/s41467-022-30174-1"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_1","DOI":"10.1016\/j.cell.2021.11.018"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_1","DOI":"10.1016\/j.autrev.2020.102647"},{"doi-asserted-by":"publisher","key":"e_1_2_10_16_1","DOI":"10.1084\/jem.20061775"},{"doi-asserted-by":"publisher","key":"e_1_2_10_17_1","DOI":"10.1016\/j.it.2016.08.012"},{"doi-asserted-by":"publisher","key":"e_1_2_10_18_1","DOI":"10.4049\/jimmunol.0901906"},{"doi-asserted-by":"publisher","key":"e_1_2_10_19_1","DOI":"10.1002\/adma.202201322"},{"doi-asserted-by":"publisher","key":"e_1_2_10_20_1","DOI":"10.1038\/s41598-019-44682-6"},{"doi-asserted-by":"publisher","key":"e_1_2_10_21_1","DOI":"10.1016\/j.bbi.2020.03.004"},{"doi-asserted-by":"publisher","key":"e_1_2_10_22_1","DOI":"10.1172\/JCI66895"},{"doi-asserted-by":"publisher","key":"e_1_2_10_23_1","DOI":"10.1186\/s40478-018-0536-y"},{"doi-asserted-by":"publisher","key":"e_1_2_10_24_1","DOI":"10.1021\/acsnano.3c04497"},{"doi-asserted-by":"publisher","key":"e_1_2_10_25_1","DOI":"10.1038\/ni1178"},{"doi-asserted-by":"publisher","key":"e_1_2_10_26_1","DOI":"10.1038\/nri2343"},{"key":"e_1_2_10_27_1","volume":"114","author":"Oh S. 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