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pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response
Liu, Qi1,2; Chen, Xiaoming1,2; Jia, Jilei1,2; Zhang, Weifeng1,2; Yang, Tingyuan1; Wang, Lianyan1; Ma, Guanghui1,3
2015-05-01
Source PublicationACS NANO
ISSN1936-0851
Volume9Issue:5Pages:4925-4938
Abstract

In the quest to treat intracellular infectious diseases and virus infection, nanoparticles (NPs) have been considered to be efficient tools for inducing potent immune responses, specifically cellular immunity. Antigen processing and presenting by antigen presenting cells (APCs) could influence immune response, especially the priming of T-cell-mediated cellular immunity. Here, we fabricated pH-responsive poly(D,L-lactic-co-glycolic acid) (PLEA) NPs with rapid antigen intracellular release behavior in APCs. The NPs, which had thin shells and large inner space, contain ammonium bicarbonate (NH4HCO3), which could regulate release in endosomes and lysosomes, acting as an antigen release promoter in dendritic cells (DCs), and were coencapsulated with antigen (ovalbumin, OVA). Hydrogen ions (H+) in DC endosomes and lysosomes (pH similar to 5.0 and 6.5) could react with NH4HCO3 to generate NH3 and CO2, which broke NPs and released antigens. After uptake by DCs, antigens encapsulated in pH-responsive PLEA NPs could escape from lysosomes into the cytoplasm and be cross-presented. Moreover, the NPs induced up-regulation of co-stimulatory molecules and stimulated cytokine production. Mouse immunization with pH-responsive PLEA NPs induced greater lymphocyte activation, more antigen-specific CD8(+) T cells, stronger cytotoxic capacity (IFN-gamma and granzyme B), enhanced antigen-specific IgG antibodies, and higher serum IgG2a/IgG1, indicating cellular immunity. The NPs also improved generation of memory T cells to protect against reinfection. Thus, pH-responsive PLEA NPs, which induced strong cellular immune responses and offered antibody protection, could be potentially useful as effective vaccine delivery and adjuvant systems for the therapy of intracellular infectious diseases and virus infection.

KeywordAntigen Intracellular Rapid Release Dendritic Cells Ph-responsive Plga Nanoparticles Vaccine Delivery And Adjuvant System
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences ; Technology
DOI10.1021/nn5066793
Indexed BySCI
Language英语
WOS KeywordT-CELL DIFFERENTIATION ; DENDRITIC CELLS ; ALUMINUM-HYDROXIDE ; CROSS-PRESENTATION ; VACCINE ADJUVANTS ; IN-VITRO ; MEMORY ; EFFECTOR ; DELIVERY ; MICROPARTICLES
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science
WOS SubjectChemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:000355383000028
Citation statistics
Cited Times:94[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/19272
Collection生化工程国家重点实验室
Affiliation1.Chinese Acad Sci, Inst Proc Engn, PLA Key Lab Biopharmaceut Prod & Formulat Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Collaborat Innovat Ctr Chem Sci & Engn Tianjin, Tianjin 300072, Peoples R China
Recommended Citation
GB/T 7714
Liu, Qi,Chen, Xiaoming,Jia, Jilei,et al. pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response[J]. ACS NANO,2015,9(5):4925-4938.
APA Liu, Qi.,Chen, Xiaoming.,Jia, Jilei.,Zhang, Weifeng.,Yang, Tingyuan.,...&Ma, Guanghui.(2015).pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response.ACS NANO,9(5),4925-4938.
MLA Liu, Qi,et al."pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response".ACS NANO 9.5(2015):4925-4938.
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