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Surface assembly of poly(I:C) on polyethyleneimine‐modified gelatin nanoparticles as immunostimulatory carriers for mucosal antigen delivery
Author(s) -
Lin ShenFu,
Jiang PingLun,
Tsai JengShiang,
Huang YiYou,
Lin ShyrYi,
Lin JiunnHorng,
Liu DerZen
Publication year - 2019
Publication title -
journal of biomedical materials research part b: applied biomaterials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.665
H-Index - 108
eISSN - 1552-4981
pISSN - 1552-4973
DOI - 10.1002/jbm.b.34215
Subject(s) - nasal administration , cd86 , ovalbumin , immune system , chemistry , cd80 , antigen , immunoadjuvant , proinflammatory cytokine , immunostimulant , antibody , mucous membrane of nose , microbiology and biotechnology , immunology , in vitro , biology , t cell , cd40 , biochemistry , inflammation , cytotoxic t cell
The mucosal immune system is the host's first line of defense against invasion by foreign pathogens. Gelatin nanoparticles (GNPs) are suitable carriers for the delivery of antigens via various routes of administration. In the present study, GNPs were modified with polyethyleneimine (PEI), a positively charged polymer. Then, ovalbumin (OVA) and polyinosinic:polycytidylic acid (poly(I:C)), an immunostimulant, were adsorbed onto the surface of the positively charged GNPs. We assessed whether GNPs could act as an effective mucosal vaccine that is capable of inducing both mucosal and systemic immune responses. The results showed that GNPs effectively adsorbed OVA/poly(I:C), facilitated cellular uptake by RAW 264.7 macrophage cells and murine bone marrow‐derived dendritic cells (BMDCs) in vitro , and led to increased expression of the maturation markers CD80 and CD86 on BMDCs. Furthermore, GNPs induced increased secretion of proinflammatory cytokines in both RAW 264.7 and BMDCs. C57BL/6 mice that were intranasally twice‐immunized with OVA/poly(I:C)‐loaded GNPs produced high levels of serum OVA‐specific IgG antibodies and secretory IgA in nasal and lung lavage. Spleen cells from immunized mice were collected and re‐stimulated with OVA, and results showed significantly augmented production of IFN‐ γ , IL‐4, IL‐5, and IL‐6 in mice that received OVA/poly(I:C)‐loaded GNPs. Moreover, intranasal immunization with OVA/poly(I:C)‐loaded GNPs resulted in the inhibition of EG7 tumor growth in C57BL/6 mice. Taken together, these results indicate that nasal administration of OVA/poly(I:C)‐loaded GNPs elicited effective mucosal and systemic immune responses, which might be useful for further applications of antigen delivery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1228–1237, 2019.