An antigen-encapsulating nanoparticle platform for T_H1/17 immune tolerance therapy

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• 作者：Derrick P. McCarthy ; PhD^a ; ¹ ; Jonathan Woon-Teck Yap ; PhD^b ; ¹ ; Christopher T. Harp ; PhD^a ; ¹ ; W. Kelsey Song ; BS^c ; Jeane Chen ; PhD^c ; Ryan M. Pearson ; PhD^g ; Stephen D. Miller ; PhD^a ; ^d ; ^e ; ^{s-d-miller@northwestern.edu} ; Lonnie D. Shea ; PhD^b ; ^c ; ^d ; ^e ; ^f ; ^g ; ^h ; ^{ldshea@umich.edu}
• 关键词：Nanoparticle ; Immune tolerance ; Autoimmune disease ; Drug delivery
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：13
• 期：1
• 页码：191-200
• 全文大小：1235 K
• 卷排序：13

文摘

Tolerogenic nanoparticles (NPs) are rapidly being developed as specific immunotherapies to treat autoimmune disease. However, many NP-based therapies conjugate antigen (Ag) directly to the NP posing safety concerns due to antibody binding or require the co-delivery of immunosuppressants to induce tolerance. Here, we developed Ag encapsulated NPs comprised of poly(lactide-co-glycolide) [PLG(Ag)] and investigated the mechanism of action for Ag-specific tolerance induction in an autoimmune model of T helper type 1/17 dysfunction – relapse-remitting experimental autoimmune encephalomyelitis (R-EAE). PLG(Ag) completely abrogated disease induction in an organ specific manner, where the spleen was dispensable for tolerance induction. PLG(Ag) delivered intravenously distributed to the liver, associated with macrophages, and recruited Ag-specific T cells. Furthermore, programmed death ligand 1 (PD-L1) was increased on Ag presenting cells and PD-1 blockade lessened tolerance induction. The robust promotion of tolerance by PLG(Ag) without co-delivery of immunosuppressive drugs, suggests that these NPs effectively deliver antigen to endogenous tolerogenic pathways.