Conjugation of Transforming Growth Factor Beta to Antigen-Loaded Poly(lactide- co-glycolide) Nanoparticles Enhances Efficiency of Antigen-Specific Tolerance.
Conjugation of Transforming Growth Factor Beta to Antigen-Loaded Poly(lactide- co-glycolide) Nanoparticles Enhances Efficiency of Antigen-Specific Tolerance.
复制标题
DOI：
10.1021/acs.bioconjchem.7b00624
复制
发表时间：
2018-03-21
影响因子：
4.7
通讯作者：
Shea LD
中科院分区：
文献类型：
--
作者：
Casey LM;Pearson RM;Hughes KR;Liu JMH;Rose JA;North MG;Wang LZ;Lei M;Miller SD;Shea LD
目前用于治疗自身免疫的策略涉及损害健康免疫的广谱免疫抑制剂的施用。静脉注射（i. v.）施用含有疾病相关抗原（Ag-NP）的聚（丙交酯-共-乙交酯）纳米颗粒（NP）已经在自身免疫模型中证明了抗原（Ag）特异性免疫耐受。然而，皮下（s.c.）Ag-NP的递送并不有效。本研究验证了免疫调节细胞因子转化生长因子β 1（TGF-β）在银纳米颗粒上的共递送将调节对银纳米颗粒的免疫应答并提高耐受诱导效率的假设。将TGF-β偶联到Ag-NP的表面，使得Ag和TGF-β的负载是独立可调的。通过减少骨髓来源的树突状细胞的炎性表型和在共培养系统中诱导调节性T细胞，该颗粒在体外证明了Ag和TGF-β的生物活性递送。使用多发性硬化、实验性自身免疫性脑脊髓炎的体内小鼠模型，在Ag-NP上的TGF-β共递送导致通过静脉内施用在较低剂量下的改善的功效和通过皮下注射显著降低的疾病严重程度。局这项研究表明，免疫调节细胞因子对银纳米颗粒的共递送可以提高Ag特异性耐受治疗的疗效，通过编程Ag呈递细胞更有效的耐受诱导。
Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide-co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen (Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that codelivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-β), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction. TGF-β was coupled to the surface of Ag-NPs such that the loadings of Ag and TGF-β were independently tunable. The particles demonstrated bioactive delivery of Ag and TGF-β in vitro by reducing the inflammatory phenotype of bone marrow-derived dendritic cells and inducing regulatory T cells in a coculture system. Using an in vivo mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis, TGF-β codelivery on Ag-NPs resulted in improved efficacy at lower doses by i.v. administration and significantly reduced disease severity by s.c. administration. This study demonstrates that the codelivery of immunomodulatory cytokines on Ag-NPs may enhance the efficacy of Ag-specific tolerance therapies by programming Ag presenting cells for more efficient tolerance induction.
登录
查看更多内容
DOI：
10.1146/annurev-bioeng-110315-020137
发表时间：
2016-07-11
影响因子：
9.7
作者：
Luo X;Miller SD;Shea LD
通讯作者：
Shea LD
影响因子：
7
作者：
Curtsinger JM;Mescher MF
通讯作者：
Mescher MF
DOI：
10.1016/j.nano.2016.01.013
发表时间：
2016-07
期刊：
Nanomedicine : nanotechnology, biology, and medicine
影响因子：
--
作者：
Park JK;Utsumi T;Seo YE;Deng Y;Satoh A;Saltzman WM;Iwakiri Y
通讯作者：
Iwakiri Y
影响因子：
17.1
作者：
Hunter Z;McCarthy DP;Yap WT;Harp CT;Getts DR;Shea LD;Miller SD
通讯作者：
Miller SD
影响因子：
4.4
作者：
Henry, Emmanuelle;Desmet, Christophe J.;Bureau, Fabrice
通讯作者：
Bureau, Fabrice