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Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines
Xu P.1; Tang S.1; Jiang L.1; Yang L.1; Zhang D.1; Feng S.1; Zhao T.1; Dong Y.1; He W.1; Wang R.4; Zhang J.1; Liang Z.1
2016-03-10
Source PublicationJournal of Controlled Release
ISSN18734995 01683659
Volume225Pages:252-258
Abstract

Nanovehicles are promising delivery systems for various vaccines. Nevertheless, different biophysicochemical properties of nanoparticles (NPs), dominating their in vitro and in vivo performances for vaccination, remain unclear. We attempted to elucidate the effects of NPs and their pH-sensitivity on in vitro and in vivo efficacy of resulting prophylactic nanovaccines containing a contraceptive peptide (FSHR). To this end, pH-responsive and non-responsive nanovaccines were produced using acetalated β-cyclodextrin (Ac-bCD) and poly(lactic-co-glycolic acid) (PLGA), respectively. Meanwhile, FSHR derived from an epitope of the follicle-stimulating hormone receptor was used as the model antigen. FSHR-containing Ac-bCD and PLGA NPs were successfully prepared by a nanoemulsion technique, leading to well-shaped nanovaccines with high loading efficiency. The pH-sensitivity of Ac-bCD and PLGA nanovaccines was examined by in vitro hydrolysis and antigen release studies. Nanovaccines could be effectively engulfed by dendritic cells (DCs) via endocytosis in both dose and time dependent manners, and their intracellular trafficking was closely related to the pH-sensitivity of the carrier materials. Furthermore, nanovaccines could induce the secretion of inflammatory cytokines by DCs and T cells co-cultured with the stimulated DCs. In vivo evaluations demonstrated that nanovaccines were more potent than that based on the complete Freund's adjuvant, with respect to inducing anti-FSHR antibody, reducing the sperm count, inhibiting the sperm motility, and increasing the teratosperm rate. Immunization of male mice with nanovaccines notably decreased the parturition incidence of the mated females. Consequently, both in vitro and in vivo activities of FSHR could be considerably augmented by NPs. More importantly, our studies indicated that the pH-responsive nanovaccine was not superior over the non-responsive counterpart for the examined peptide antigen.

KeywordCyclodextrin Dendritic Cell Intracellular Delivery Nanoparticle Peptide Antigen Ph-responsive
DOI10.1016/j.jconrel.2016.01.043
URLView the original
Indexed BySCI
WOS Research AreaChemistry ; Pharmacology & Pharmacy
WOS SubjectChemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS IDWOS:000371054900021
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Third Military Medical University
2.Tangshan Workers' Hospital of Hebei Province
3.81 Hospital of PLA
4.University of Macau
Recommended Citation
GB/T 7714
Xu P.,Tang S.,Jiang L.,et al. Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines[J]. Journal of Controlled Release,2016,225:252-258.
APA Xu P..,Tang S..,Jiang L..,Yang L..,Zhang D..,...&Liang Z..(2016).Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines.Journal of Controlled Release,225,252-258.
MLA Xu P.,et al."Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines".Journal of Controlled Release 225(2016):252-258.
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