Engineering biodegradable guanidyl-decorated PEG-PCL nanoparticles as robust exogenous activators of DCs and antigen cross-presentation,Nanoscale

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Engineering biodegradable guanidyl-decorated PEG-PCL nanoparticles as robust exogenous activators of DCs and antigen cross-presentation
Nanoscale ( IF 5.8 ) Pub Date : 2017-09-06 00:00:00 , DOI: 10.1039/c7nr04470d
Pan Li _{1,

2,

3,

4,

5} , Huijuan Song _{1,

2,

3,

4,

5} , Hao Zhang _{5,

6,

7} , Pengxiang Yang _{1,

2,

3,

4,

5} , Chuangnian Zhang _{1,

2,

3,

4,

5} , Pingsheng Huang _{1,

2,

3,

4,

5} , Deling Kong _{1,

2,

3,

4,

5} , Weiwei Wang _{1,

2,

3,

4,

5}

Affiliation

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.

中文翻译：

将可生物降解的胍基修饰的PEG-PCL纳米颗粒工程化为DC的强大外源性激活剂和抗原交叉呈递

基于纳米颗粒（NPs）的佐剂在疫苗的开发中引起了广泛的关注。以前，我们首次报道了一种用作抗原传递载体的胍基修饰的聚合物NP。但是，其不可降解性可能会限制潜在的临床翻译。更重要的是，树突状细胞（DC）吞噬这些NP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然不清楚。这里，我们显示的NP组装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）（的mPEG- b -PCL-克-PGEM，PECG）共聚物可以牢固地激活DC，并促进其成熟；另外，在体外和体内都改善了抗原交叉呈递。重要的是，我们的研究结果还表明，通过调节细胞因子（包括IFN-γ和TNF-α）的分泌，纳米颗粒表面胍基的增加可调节PECG NPs佐剂的储库作用和淋巴结引流以及免疫反应。我们的研究提供了胍基修饰的纳米佐剂和新型佐剂对含蛋白抗原疫苗的作用的见解。我们预期胍基修饰的策略将成为开发更多令人兴奋的免疫佐剂的起点。

更新日期：2017-09-21

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