Bioconjugate Chem. 2009, 20, 111–119
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T-Cell Activation by Antigen-Loaded pH-Sensitive Hydrogel Particles in ViWo: The Effect of Particle Size Joel A. Cohen,† Tristan T. Beaudette,† William W. Tseng,‡ Eric M. Bachelder,† Ines Mende,‡ Edgar G. Engleman,‡ and Jean M. J. Fre´chet†,* College of Chemistry, University of California, Berkeley, California, 94720-1460, and Department of Pathology, Stanford University School of Medicine, Palo Alto, California. Received August 6, 2008; Revised Manuscript Received October 9, 2008
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 antigenpresenting 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 µm 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.
INTRODUCTION The physical dimensions of a biomaterial are key parameters that may dictate the interaction of the material with its surrounding biological environment, particularly when those dimensions are on the micro- or the nanoscale. For example, while many cell types are capable of ingesting small-sized particulate matter (typically
