利用浸浴后的成年斑马鱼粘膜性树突状细胞分析不含表面活性剂的聚乳酸纳米疫苗载体的特异性和有效性

Specific and Efficient Uptake of Surfactant-Free Poly(Lactic Acid) Nanovaccine Vehicles by Mucosal Dendritic Cells in Adult Zebrafish after Bath Immersion

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中文摘要:研究分析了粘膜免疫后,不含表面活性剂的聚乳酸纳米颗粒(PLA-NPs)能够通过自发模式靶定抗原呈递细胞(APCs)。试验利用组织学和流动成像技术,描述和定量分析了200 nm PLA-NPs在成年斑马鱼中的应用效率。在粘膜组织中,PLA-NPs在腮和皮肤表面的DC细胞、巨噬细胞和IgZ(+)B细胞等抗原呈递细胞中富集,并能特异性地被吞噬细胞中的这些抗原呈递细胞获取,而中性粒细胞中未检测到PLA-NPs。对腮的定量分析表明,DCs获取PLA-NPs的效率最高。这些结果表明,不含表面活性剂的PLA-NPs表现出理想的生物适应性,在粘膜免疫后能高效地自发靶定DCs;在医学和兽医领域,特别是水产养殖领域,PLA-NPs是理想的粘膜疫苗传递系统。
 
外文摘要:Activation of mucosal immunity is a key milestone for next-generation vaccine development. Biocompatible polymer-based nanoparticles (NPs) are promising vectors and adjuvants for mucosal vaccination. However, their in vivo uptake by mucosae and their biodistribution in antigen-presenting cells (APCs) need to be better understood to optimize mucosal nanovaccine designs. Here, we assessed if APCs are efficiently targeted in a spontaneous manner by surfactant-free poly(lactic acid) nanoparticles (PLA-NPs) after mucosal administration. Combining histology and flow imaging approaches, we describe and quantify the mucosal uptake of 200 nm PLA-NPs in adult zebrafish. Following bath administration, PLA-NPs penetrated and crossed epithelial barriers from all exposed mucosae. In mucosae, PLA-NPs accumulated in APCs, which were identified as dendritic cells (DCs), macrophages, and IgZ(+) B cells in gills and skin. PLA-NP uptake by phagocytes was specific to these cell types, as PLA-NPs were not detected in neutrophils. Importantly, quantitative analyses in gills revealed that DCs take up PLA-NPs with specifically high efficiency. This study shows that surfactant-free PLA-NPs, which display optimal biocompatibility, can spontaneously target DCs with high efficiency in vivo following mucosal administration, and highlights PLA-NPs as powerful platforms for mucosal vaccine delivery in the medical and veterinary fields, and particularly in aquaculture.
外文关键词:poly(D;L-lactic acid) nanoparticles; surfactant free; zebrafish; vaccines carrier; mucosal delivery; dendritic cells; imaging flow cytometry; biodistribution
作者:Resseguier, J; Delaune, E; Coolen, AL; Levraud, JP; Boudinot, P; Le Guellec, D; Verrier, B
作者单位:克劳德-里昂-伯纳德大学
期刊名称:FRONTIERS IN IMMUNOLOGY
期刊影响因子:5.695
出版年份:2017
出版刊次:2
点击下载:利用浸浴后的成年斑马鱼粘膜性树突状细胞分析不含表面活性剂的聚乳酸纳米疫苗载体的特异性和有效性
  1. 编译服务:动物支原体学
  2. 编译者:程金花
  3. 编译时间:2017-03-30