Exploiting the Lymph-Node-Amplifying Effect for Potent Systemic and Gastrointestinal Immune Responses via Polymer/Lipid Nanoparticles

doi:10.1021/acsnano.9b04071

	Exploiting the Lymph-Node-Amplifying Effect for Potent Systemic and Gastrointestinal Immune Responses via Polymer/Lipid Nanoparticles
	Du, Yiqun 4; Xia, Yufei 1,2; Zou, Yongjuan 1,2; Hu, Yuning 1,2; Fu, Jiaqi 1; Wu, Jie 1,3; Gao, Xiao-Dong 4; Ma, Guanghui 1,2,3
刊名	ACS NANO
	2019-12-01
卷号	13 期号:12 页码:13809-13817
关键词	polymer/lipid nanoparticles systemic and gastrointestinal immunity all-trans retinoic acid CpG-ODN lymph-node-amplifying effect
ISSN号	1936-0851
DOI	10.1021/acsnano.9b04071
英文摘要	Parenteral vaccinations are not able to elicit effective systemic and gastrointestinal immune protection simultaneously because the lymphocytes are typically restricted to primed tissues. Although all-trans retinoic acid (atRA) was reported to trigger the gut-homing of immunocytes, the bioavailability and systemic immune responses remain limited for use in robust enteric vaccinations. Here, we show that co-delivery of atRA, CpG oligodeoxynucleotides (CpG), and antigens via engineered polymer/lipid nanoparticles (PLNPs) could exploit the amplifying function of draining lymph nodes (DLNs) for potent gut tropism and immune activations. After intramuscular injection, forming an immune-potentiated environment at the injection site, the PLNPs induced the designated transfer of primed dendritic cells (DCs) to the DLNs instead of the gastrointestinal tissues. Within the DLNs, the immune-potentiated environment markedly amplified the antigen presentation and homing receptor switch among immunocytes, which simultaneously stimulated the preferential dissipation of activated lymphocytes in the peripheral and gastrointestinal tissues, that is, exerted a DLN-amplifying effect. Compared with current atRA-containing formulations, the PLNPs not only boosted potent IgG secretions and T cell activations in the peripheral tissue but also provoked robust T cell homing and antigen-specific IgA levels in the gastrointestinal tracts in both ovalbumin and EV71 vaccinations. These data indicate that exploiting DLN amplification can stimulate potent systemic and gastrointestinal responses for more efficient enteric vaccinations.
资助项目	Pilot Project of Chinese Academy of Sciences[XDB29040303] ; Foundation for Innovative Research Groups of the National Natural Science Foundation of China[21821005] ; National Natural Science Foundation of China[21776287] ; National Natural Science Foundation of China[21576268] ; National Natural Science Foundation of China[21778023] ; National Natural Science Foundation of China[21908229] ; Program of Introducing Talents of Discipline to Universities[111-2-06] ; National First-class Discipline Program of Light Industry Technology and Engineering[LITE2018-015] ; Chinese Academy of Sciences[ZDBS-LY-SLH040] ; Open Funding Project of the State Key Laboratory of Biochemical Engineering[2014KF-02]
WOS关键词	RETINOIC ACID ; GUT ; VACCINES ; IMMUNIZATION ; MIGRATION ; DELIVERY ; RELEASE ; CELLS
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000505633300021
资助机构	Pilot Project of Chinese Academy of Sciences ; Foundation for Innovative Research Groups of the National Natural Science Foundation of China ; National Natural Science Foundation of China ; Program of Introducing Talents of Discipline to Universities ; National First-class Discipline Program of Light Industry Technology and Engineering ; Chinese Academy of Sciences ; Open Funding Project of the State Key Laboratory of Biochemical Engineering
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/38614]
专题	中国科学院过程工程研究所
通讯作者	Wu, Jie; Gao, Xiao-Dong; Ma, Guanghui
作者单位	1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100190, Peoples R China 3.Chinese Acad Sci, PLA Key Lab Biopharmaceut Prod & Formulat Engn, Inst Proc Engn, Beijing 100190, Peoples R China 4.Jiangnan Univ, Key Lab Carbohydrate Chem & Biotechnol, Minist Educ, Sch Biotechnol, Wuxi 214122, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Du, Yiqun,Xia, Yufei,Zou, Yongjuan,et al. Exploiting the Lymph-Node-Amplifying Effect for Potent Systemic and Gastrointestinal Immune Responses via Polymer/Lipid Nanoparticles[J]. ACS NANO,2019,13(12):13809-13817.
APA	Du, Yiqun.,Xia, Yufei.,Zou, Yongjuan.,Hu, Yuning.,Fu, Jiaqi.,...&Ma, Guanghui.(2019).Exploiting the Lymph-Node-Amplifying Effect for Potent Systemic and Gastrointestinal Immune Responses via Polymer/Lipid Nanoparticles.ACS NANO,13(12),13809-13817.
MLA	Du, Yiqun,et al."Exploiting the Lymph-Node-Amplifying Effect for Potent Systemic and Gastrointestinal Immune Responses via Polymer/Lipid Nanoparticles".ACS NANO 13.12(2019):13809-13817.