Polyanhydride microparticles enhance dendritic cell antigen presentation and activation.

María del Pilar Torres-González's picture
PDF versionPDF version
TitlePolyanhydride microparticles enhance dendritic cell antigen presentation and activation.
Publication TypeJournal Article
Year of Publication2011
AuthorsTorres, MP, Wilson-Welder, JH, Lopac, SK, Phanse, Y, Carrillo-Conde, B, Ramer-Tait, AE, Bellaire, BH, Wannemuehler, MJ, Narasimhan, B
JournalActa Biomater
Date Published2011 Jul
KeywordsAdjuvants, Immunologic, Animals, Antigen Presentation, Bone Marrow Cells, Cells, Cultured, Cytokines, Dendritic Cells, Female, Genes, MHC Class II, Humans, Male, Materials Testing, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Molecular Structure, Particle Size, Polyanhydrides, Polymers, T-Lymphocytes

The present study was designed to evaluate the adjuvant activity of polyanhydride microparticles prepared in the absence of additional stabilizers, excipients or immune modulators. Microparticles composed of varying ratios of either 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic acid or 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane and CPH were added to in vitro cultures of bone marrow-derived dendritic cells (DCs). Microparticles were efficiently and rapidly phagocytosed by DCs in the absence of opsonization and without centrifugation or agitation. Within 2h, internalized particles were rapidly localized to an acidic, phagolysosomal compartment. By 48 h, only a minor reduction in microparticle size was observed in the phagolysosomal compartment, indicating minimal particle erosion consistent with being localized within an intracellular microenvironment favoring particle stability. Polyanhydride microparticles increased DC surface expression of major histocompatability complex class II, the co-stimulatory molecules CD86 and CD40, and the C-type lectin CIRE (murine DC-SIGN; CD209). In addition, microparticle stimulation of DCs also enhanced secretion of the cytokines IL-12p40 and IL-6, a phenomenon found to be dependent on polymer chemistry. DCs cultured with polyanhydride microparticles and ovalbumin induced polymer chemistry-dependent antigen-specific proliferation of both CD4(+) OT-II and CD8(+) OT-I T cells. These data indicate that polyanhydride particles can be tailored to take advantage of the potential plasticity of the immune response, resulting in the ability to induce immune protection against many types of pathogens.

Alternate JournalActa Biomater
PubMed ID21439412
PubMed Central IDPMC3710784
Grant ListF31 CA126533-02 / CA / NCI NIH HHS / United States