Surface assembly of poly(I:C) on polyethyleneimine-modified gelatin nanoparticles as immunostimulatory carriers for mucosal antigen delivery
Journal
Journal of Biomedical Materials Research - Part B Applied Biomaterials
Journal Volume
107
Journal Issue
4
Pages
1228-1237
Date Issued
2019
Author(s)
Abstract
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. ? 2018 Wiley Periodicals, Inc.
Subjects
antigen delivery; gelatin nanoparticles; mucosal immunity; ovalbumin; polyinosinic:polycytidylic acid
SDGs
Other Subjects
Antigens; Immunization; Mammals; Nanoparticles; Antigen delivery; Gelatin nanoparticles; Intranasal immunizations; Mucosal immunity; Nasal administration; Ovalbumins; Pro-inflammatory cytokines; Raw 264.7 macrophages; Immune system; B7 antigen; cancer vaccine; CD86 antigen; gamma interferon; gelatin; immunoglobulin G antibody; interleukin 4; interleukin 5; interleukin 6; nanocarrier; ovalbumin; polyethyleneimine; polyinosinic polycytidylic acid; secretory immunoglobulin; antigen; cytokine; drug carrier; gelatin; immunological adjuvant; nanoparticle; polyethyleneimine; polyinosinic polycytidylic acid; animal cell; animal experiment; animal model; animal tissue; antibody blood level; antibody response; Article; bone marrow derived macrophage; cancer immunization; cell maturation; controlled study; cross linking; cytokine production; cytokine release; enzyme linked immunosorbent assay; female; in vitro study; lymphoma; mouse; nonhuman; particle size; photon correlation spectroscopy; RAW 264.7 cell line; secondary immunization; surface property; vaccination; animal; bone marrow cell; chemistry; dendritic cell; drug absorption; drug effect; immunization; immunology; intranasal drug administration; mucosal immunity; Adjuvants, Immunologic; Administration, Intranasal; Animals; Antigens; Bone Marrow Cells; Cytokines; Dendritic Cells; Drug Carriers; Female; Gelatin; Immunity, Mucosal; Immunization; Mice; Nanoparticles; Nasal Absorption; Poly I-C; Polyethyleneimine; RAW 264.7 Cells
Type
journal article