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Immunosuppressive drugs, such as FTY720, are subsequently developed to prevent the migration of CD4<jats:sup>+<\/jats:sup> T lymphocytes to the central nervous system (CNS). However, these immunosuppressive drugs have limited accumulation in lymph nodes (LNs), resulting in poor efficacy. Here, this work develops a nanoplatform for delivering immunosuppressive drugs to LNs for durable MS treatment. Human CD47 peptide and L\u2010selectin targeting aptamer are modified on the nanoparticles encapsulated with FTY720 (clnFTY) for self\u2010passivation and the targeting of L\u2010selectin on lymphocytes, a homing receptor for T\u2010cells entering LNs. Using this natural process, clnFTY nanoparticles efficiently deliver FTY720 to LNs and delay disease progression in experimental autoimmune encephalomyelitis (EAE) mice following a single dose treatment over a 42\u2010day observational period. Considering the daily dosing requirement of FTY720, this strategy greatly improves its therapeutic efficiency. The ability of clnFTY nanoparticles to target lymphocytes, reduce sphingosine\u20101\u2010phosphate receptor 1 (S1PR1) expression, and suppress inflammatory cytokines release are demonstrated in clinical blood samples from MS patients. Taken together, this study demonstrates that targeted LNs delivery may greatly extend the treatment cycle of immunosuppressive drugs for durable MS treatment.<\/jats:p>","DOI":"10.1002\/advs.202300738","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T03:33:22Z","timestamp":1683862402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting L\u2010Selectin Lymphocytes to Deliver Immunosuppressive Drug in Lymph Nodes for Durable Multiple Sclerosis Treatment"],"prefix":"10.1002","volume":"10","author":[{"given":"Yipeng","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Neurology The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510000 China"},{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterials &amp; Nanosafety CAS Center for Excellence in Nanoscience National Center for Nanoscience and Technology  Beijing 100190 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