Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.
Nanoscale. 2017 Sep 21;9(36):13413-13418. doi: 10.1039/c7nr04470d.
Nanoparticles (NPs)-based adjuvants are attracting much attention in the development of vaccines. Previously, we reported a type of guanidyl-decorated polymeric NPs used as antigen delivery carriers for the first time. However, its un-degradability may restrict potential clinical translation. More importantly, the specific cellular pathway by which dendritic cells (DCs) endocytosed these NPs and the relationship among guanidyl with the antigen cross-presentation, cytokine secretion, and lymph node targeting still remain unclear. Here, we show NPs assembled by biodegradable methoxyl poly(ethylene glycol)-block-poly(ε-caprolactone)-graft-poly(2-(guanidyl) ethyl methacrylate) (mPEG-b-PCL-g-PGEM, PECG) copolymers can robustly activate DCs and promote their maturation; additionally antigen cross-presentation was improved both in vitro and in vivo. Significantly, our results also demonstrate the increase of surface guanidyl on nanoparticles modulates the depot effect and lymph node drainage of PECG NPs-based adjuvants, as well as immune responses, by regulating the secretion of cytokines including IFN-γ and TNF-α. Our study provides insights into the action of guanidyl-decorated nanoscale adjuvants and new adjuvants for vaccines containing protein antigens. We anticipate the strategy of guanidyl decoration to be a starting point for the development of more exciting immunoadjuvants.
基于纳米粒子 (NPs) 的佐剂在疫苗开发中引起了广泛关注。此前，我们首次报道了一种胍基修饰的聚合物 NPs，用作抗原递送载体。然而，其不可降解性可能限制其在潜在临床转化中的应用。更重要的是，树突状细胞 (DCs) 内吞这些 NPs 的具体细胞途径，以及胍基与抗原交叉呈递、细胞因子分泌和淋巴结靶向之间的关系仍不清楚。在这里，我们展示了由可生物降解的甲氧基聚乙二醇-嵌段-聚(ε-己内酯)-接枝-聚(2-(胍基)乙基甲基丙烯酸酯)(mPEG-b-PCL-g-PGEM，PECG)共聚物组装的 NPs 可以强烈激活 DCs 并促进其成熟;此外，抗原交叉呈递在体外和体内都得到了改善。值得注意的是，我们的结果还表明，纳米粒子表面胍基的增加通过调节 IFN-γ 和 TNF-α 等细胞因子的分泌，调节 PECG NPs 佐剂的储存效应和淋巴结引流以及免疫反应。我们的研究为胍基修饰的纳米级佐剂的作用以及含有蛋白质抗原的疫苗的新型佐剂提供了新的见解。我们预计胍基修饰策略将成为开发更令人兴奋的免疫佐剂的起点。
