The induction of an antigen-specific adaptive immune response exclusively occurs in lymphoid organs. As a consequence, the efficacy with which vaccines reach these immune-inducing sites strongly affects the protective efficacy of the vaccine. Here, we report the design of redox-sensitive polymer hydrogel nanoparticles that efficiently target multiple immune cell subsets in the draining lymph nodes. Nanoparticles are fabricated by infiltrating mesoporous silica particles (~200 nm) with poly(methacrylic acid) followed by disulfide-based crosslinking and template removal. PEGylation of these nanoparticles does not affect their cellular association <i>in vitro</i>, but dramatically improves their lymphatic drainage <i>in vivo</i>, as elucidated by flow cytometry and confocal fluorescence microscopy. The functional relevance of these observations is further illustrated by the increased priming of antigen-specific T cells. Our findings highlight the potential of engineered hydrogel nanoparticles for the lymphatic delivery of antigens and immune-modulating compounds.

Engineering polymer hydrogel nanoparticles for lymph node targeted vaccine delivery

251st National Meeting (2016)

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