Polyanhydride microparticles enhance dendritic cell antigen presentation and activation

Maria P. Torres, Jennifer H. Wilson-Welder, Senja K. Lopac, Yashdeep Phanse, Brenda Carrillo-Conde, Amanda E. Ramer-Tait, Bryan H. Bellaire, Michael J. Wannemuehler, Balaji Narasimhan

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

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 2 h, 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.

Original languageEnglish (US)
Pages (from-to)2857-2864
Number of pages8
JournalActa Biomaterialia
Volume7
Issue number7
DOIs
StatePublished - Jul 1 2011

Keywords

  • Adjuvants
  • Dendritic cells
  • Microparticles
  • Polyanhydrides
  • Vaccine delivery

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

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  • Cite this

    Torres, M. P., Wilson-Welder, J. H., Lopac, S. K., Phanse, Y., Carrillo-Conde, B., Ramer-Tait, A. E., Bellaire, B. H., Wannemuehler, M. J., & Narasimhan, B. (2011). Polyanhydride microparticles enhance dendritic cell antigen presentation and activation. Acta Biomaterialia, 7(7), 2857-2864. https://doi.org/10.1016/j.actbio.2011.03.023