The incorporation of cationic property and immunopotentiator in poly (lactic acid) microparticles promoted the immune response against chronic hepatitis B
文献类型:期刊论文
作者 | Lu, Ting1,2; Hu, Fumin1,2; Yue, Hua1; Yang, Tingyuan1; Ma, Guanghui1,2,3 |
刊名 | JOURNAL OF CONTROLLED RELEASE
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出版日期 | 2020-05-10 |
卷号 | 321页码:576-588 |
关键词 | Poly (lactic acid) uniform microparticles Cationic DDAB STING agonist Chronic hepatitis B model mice Therapeutic vaccine |
ISSN号 | 0168-3659 |
DOI | 10.1016/j.jconrel.2020.02.039 |
英文摘要 | Biodegradable microparticles (MPs) as vaccine adjuvants have sparked the passion of researchers in recent decades. However, it is still a huge challenge to develop an efficient vaccine delivery system to reverse chronic hepatitis B (CHB). Herein, we integrated a physiochemical merit and an immunopotentiator property in poly (lactic acid) (PLA) MPs and verified the therapeutic effect on CHB model mice. We prepared uniform MPs with insertion of cationic lipid didodecyldimethylammonium bromide (DDAB), which endowed a physiochemical merit for MPs. Such a DDAB-PLA (DP) group raised the recruitment of immune cells to the injection site along with the secretion of chemokines and pro-inflammatory cytokines, promoting the activation of antigen-presenting cells (APCs). Further combination of stimulator of interferon genes (STING) agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) (DP-D) elevated 5.8-fold higher interferon regulatory factor 7 (IRF-7) expression compared to that for DP group. The DP group showed preferred lysosome escape advantage, which was in line with the DMXAA release behavior and the intracellular target of DMXAA. In addition, DP-D vaccine augmented the IFN-gamma secreting splenocytes and motivated Th1-biased antibodies in a more efficient way than that for the DP group. In the CHB model, the MPs based vaccines achieved 50% HBsAg seroconversion rate, and HBcAg in the liver also got a reduction. DP-D produced higher amount of memory T/B cells to confer protection in a sustained manner. Present work thus provided a promising strategy, via integrating a fine-tuned physiochemical property and an immunopotentiator virtue in the MPs, which synergistically reinforced both humoral and cellular immune responses against CHB. |
WOS关键词 | MOUSE MODEL ; CELL-DIFFERENTIATION ; HYBRID NANOPARTICLES ; PLA NANOPARTICLES ; ADJUVANT ; MICROSPHERES ; TOLERANCE ; TRAFFICKING ; RECRUITMENT ; EFFECTOR |
资助项目 | National Natural Science Foundation of China (NSFC) project[21821005] ; National Science and Technology Major Project of China[2014ZX09102045] |
WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
语种 | 英语 |
WOS记录号 | WOS:000526179100040 |
出版者 | ELSEVIER |
资助机构 | National Natural Science Foundation of China (NSFC) project ; National Science and Technology Major Project of China |
源URL | [http://ir.ipe.ac.cn/handle/122111/39994] ![]() |
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 | Lu, Ting,Hu, Fumin,Yue, Hua,et al. The incorporation of cationic property and immunopotentiator in poly (lactic acid) microparticles promoted the immune response against chronic hepatitis B[J]. JOURNAL OF CONTROLLED RELEASE,2020,321:576-588. |
APA | Lu, Ting,Hu, Fumin,Yue, Hua,Yang, Tingyuan,&Ma, Guanghui.(2020).The incorporation of cationic property and immunopotentiator in poly (lactic acid) microparticles promoted the immune response against chronic hepatitis B.JOURNAL OF CONTROLLED RELEASE,321,576-588. |
MLA | Lu, Ting,et al."The incorporation of cationic property and immunopotentiator in poly (lactic acid) microparticles promoted the immune response against chronic hepatitis B".JOURNAL OF CONTROLLED RELEASE 321(2020):576-588. |
入库方式: OAI收割
来源:过程工程研究所
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