Cytosolic delivery of HBsAg and enhanced cellular immunity by pH-responsive liposome

doi:10.1016/j.jconrel.2020.05.042

	Cytosolic delivery of HBsAg and enhanced cellular immunity by pH-responsive liposome
	Hu, Fumin 1,2; Yue, Hua 1; Lu, Ting 1,2; Ma, Guanghui 1,2,3
刊名	JOURNAL OF CONTROLLED RELEASE
	2020-08-10
卷号	324 页码:460-470
关键词	pH-responsive Membrane fusion HBsAg CTLs Vaccine delivery
ISSN号	0168-3659
DOI	10.1016/j.jconrel.2020.05.042
英文摘要	It remains a major challenge to prime the cytotoxic T lymphocytes (CTLs) response for the treatment of Hepatitis B virus (HBV) infection. Inspired by an important natural biological behavior, membrane fusion, we constructed a pH-responsive nanocarrier (HBsAg&CpG@Lip) with a membrane fusion capacity for HBsAg intracellular delivery and subsequent process of CTLs. In the in vitro experiments, HBsAg&CpG@Lip greatly promoted the cellular uptake of HBsAg and the activation of BMDCs. It induced the cytosolic release of HBsAg in BMDCs, which was in conformity with the membrane fusion capacity of HBsAg&CpG@Lip. Such a capacity was improved by 4.4-fold in pH = 5.0 than that in pH = 7.4 at 60 min, which was calculated through fluorescence resonance energy transfer (FRET) efficiency. Furthermore, the cross-presentation activity induced by liposome at 1 mu g/mL was equivalent to that by soluble antigen at 2000 mu g/mL, which indicated an advantage for the liposome in cytosolic antigen delivery and potent CTLs activation. In respect of the transport of liposomes into draining lymph nodes (DLNs), the recruitment of liposome(+)migratory DCs at 24 h raised 11-fold than that at 3 h, suggesting that liposomes were mainly carried by migratory DCs. Meanwhile, HBsAg&CpG@Lip also elicited the activation of DCs and the generation of T-fh cells in DLNs. After immunization, HBsAg&CpG@Lip induced a higher anti-HBsAg IgG and ratio of IgG2c/IgG1 than that by HBsAg or Alum+HBsAg group. It also augmented a strong CTLs response as expected. Specifically, stimulation with HBsAg&CpG@Lip increased the number of IFN-gamma-secreting splenocytes, the proportion of CD107 alpha(+)CD8(+)and FasL(+)CD8(+) T cells and the secretion of Granzyme B, which verified the design of membrane fusion in vivo. In summary, this design for HBsAg cytosolic delivery exhibits great benefits for triggering CTLs, opening an avenue for the development of a potent therapeutic HBV vaccine.
资助项目	National Natural Science Foundation of China (NSFC) project[21821005] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB29040303] ; National Science and Technology Major Project of China[2014ZX09102045] ; Beijing Municipal Natural Science Foundation, China[2202056]
WOS关键词	SENSITIVE LIPOSOMES ; DENDRITIC CELLS ; RECEPTOR 9 ; T-CELLS ; NANOPARTICLES ; VACCINE ; ANTIGEN ; DIFFERENTIATION ; ACTIVATION ; RELEASE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ELSEVIER
WOS记录号	WOS:000558631400010
资助机构	National Natural Science Foundation of China (NSFC) project ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Science and Technology Major Project of China ; Beijing Municipal Natural Science Foundation, China
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/41642]
专题	中国科学院过程工程研究所
通讯作者	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 100049, Peoples R China 3.Jiangsu Natl Synerget Innovat Ctr Adv Mat, Nanjing 211816, Peoples R China
推荐引用方式 GB/T 7714	Hu, Fumin,Yue, Hua,Lu, Ting,et al. Cytosolic delivery of HBsAg and enhanced cellular immunity by pH-responsive liposome[J]. JOURNAL OF CONTROLLED RELEASE,2020,324:460-470.
APA	Hu, Fumin,Yue, Hua,Lu, Ting,&Ma, Guanghui.(2020).Cytosolic delivery of HBsAg and enhanced cellular immunity by pH-responsive liposome.JOURNAL OF CONTROLLED RELEASE,324,460-470.
MLA	Hu, Fumin,et al."Cytosolic delivery of HBsAg and enhanced cellular immunity by pH-responsive liposome".JOURNAL OF CONTROLLED RELEASE 324(2020):460-470.