Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro
Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro
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DOI：
10.1016/j.jconrel.2010.02.013
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发表时间：
2010-06-01
影响因子：
10.8
通讯作者：
Figdor, Carl G.
中科院分区：
文献类型：
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作者：
Cruz, Luis J.;Tacken, Paul J.;Figdor, Carl G.
通过抗体介导的疫苗组分靶向树突状细胞（DC）（其是专职抗原呈递细胞）来强烈增强疫苗功效。然而，将抗原或免疫调节剂连接到单个抗体的选择是有限的。在这里，我们设计了多功能的纳米和微米大小的缓释疫苗载体，专门针对人类DC，以克服这一限制。纳米（NP）和微粒（MP）的直径约为200 nm和2 μ m，由包被有携带人源化靶向抗体hD 1的聚乙二醇-脂质层的PLGA核心组成，hD 1不与补体或Fc受体相互作用，并识别DC上的人C型凝集素受体DC-SIGN。我们研究了这些颗粒如何与人DC和血细胞相互作用，以及DC内PLGA包封的抗原降解的动力学。抗原包封导致近38%的降解颗粒摄入后6天，由DC的NP和MP，相比之下，94%，当使用未包封，可溶性抗原。与非特异性地摄取的MP相反，NP有效地靶向人DC。因此，靶向递送仅改善了NP的抗原呈递，并在比非靶向NP低10-100倍的浓度下诱导抗原依赖性T细胞应答。(C)2010 Elsevier B. V.保留所有权利。
Vaccine efficacy is strongly enhanced by antibody-mediated targeting of vaccine components to dendritic cells (DCs), which are professional antigen presenting cells. However, the options to link antigens or immune modulators to a single antibody are limited. Here, we engineered versatile nano- and micrometer-sized slow-release vaccine delivery vehicles that specifically target human DCs to overcome this limitation. The nano- (NPs) and microparticles (MPs), with diameters of approximately 200 nm and 2 mu m, consist of a PLGA core coated with a polyethylene glycol-lipid layer carrying the humanized targeting antibody hD1, which does not interact with complement or Fc receptors and recognizes the human C-type lectin receptor DC-SIGN on DCs. We studied how these particles interact with human DCs and blood cells, as well as the kinetics of PLGA-encapsulated antigen degradation within DCs. Encapsulation of antigen resulted in almost 38% degradation for both NPs and MPs 6 days after particle ingestion by DCs, compared to 94% when nonencapsulated, soluble antigen was used. In contrast to the MPs, which were taken up rather nonspecifically, the NPs effectively targeted human DCs. Consequently, targeted delivery only improved antigen presentation of NPs and induced antigen-dependent T cell responses at 10-100 fold lower concentrations than nontargeted NPs. (C) 2010 Elsevier B.V. All rights reserved.