title: T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the effect of particle size.
abstract: Polymeric carriers designed to encapsulate protein antigens have great potential for improving the efficacy of vaccines and immunotherapeutics for diseases such as cancer. We recently developed a carrier system based on polyacrylamide hydrogel microparticles cross-linked with acid-labile moieties. After being phagocytosed by antigen-presenting cells, the protein encapsulated within the carrier is released and processed for subsequent presentation of antigenic epitopes. To understand the impact of particle size on the activation of T-cells following uptake by antigen-presenting cells, particles with mean diameters of 3.5 microm and 35 nm encapsulating a model protein antigen were synthesized by emulsion and microemulsion based polymerization techniques, respectively. In vivo tests demonstrated that both sizes of particles were effective at stimulating the proliferation of T-cells and were capable of generating an antigen-specific cytotoxic T-cell response when coadministered with immunostimulatory DNA. Contrary to previous reports in the literature, our results suggest that there is no significant difference in the magnitude of T-cell activation for the two sizes of particles used in these experiments. This disparity in findings may be related to fundamental differences in material properties of the carriers used in these studies, such as the hydrophilicity of the polyacrylamide particles described here versus the hydrophobic nature of carriers investigated by other groups.
authors.affiliation: College of Chemistry, University of California, Berkeley, California 94720-1460, USA.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cohen
authors.forename: Tristan T
authors.initials: TT
authors.lastname: Beaudette
authors.forename: William W
authors.initials: WW
authors.lastname: Tseng
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bachelder
authors.forename: Ines
authors.initials: I
authors.lastname: Mende
authors.forename: Edgar G
authors.initials: EG
authors.lastname: Engleman
authors.forename: Jean M J
authors.initials: JM
authors.lastname: Fréchet
mesh_terms: D000180:Acrylic Resins / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008213:Lymphocyte Activation / Q000187:drug effects*; D010316:Particle Size; D013601:T-Lymphocytes / Q000276:immunology*; D014612:Vaccines / Q000737:chemistry
chemical_list: D000180:Acrylic Resins; D000941:Antigens; D004337:Drug Carriers; D014612:Vaccines; C016680:polyacrylamide gels; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate