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The incorporation of cationic property and immunopotentiator in poly (lactic acid) microparticles promoted the immune response against chronic hepatitis B
Lu, Ting1,2; Hu, Fumin1,2; Yue, Hua1; Yang, Tingyuan1; Ma, Guanghui1,2,3
2020-05-10
Source PublicationJOURNAL OF CONTROLLED RELEASE
ISSN0168-3659
Volume321Pages:576-588
AbstractBiodegradable 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.
KeywordPoly (lactic acid) uniform microparticles Cationic DDAB STING agonist Chronic hepatitis B model mice Therapeutic vaccine
DOI10.1016/j.jconrel.2020.02.039
Language英语
WOS KeywordMOUSE MODEL ; CELL-DIFFERENTIATION ; HYBRID NANOPARTICLES ; PLA NANOPARTICLES ; ADJUVANT ; MICROSPHERES ; TOLERANCE ; TRAFFICKING ; RECRUITMENT ; EFFECTOR
Funding ProjectNational Natural Science Foundation of China (NSFC) project[21821005] ; National Science and Technology Major Project of China[2014ZX09102045]
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
Funding OrganizationNational Natural Science Foundation of China (NSFC) project ; National Science and Technology Major Project of China
WOS IDWOS:000526179100040
PublisherELSEVIER
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Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/39995
Collection中国科学院过程工程研究所
Corresponding AuthorMa, Guanghui
Affiliation1.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
Recommended Citation
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.
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