Mannose-Functionalized “Pathogen-like” Polyanhydride Nanoparticles Target C-Type Lectin Receptors on Dendritic Cells
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Targeting pathogen recognition receptors on
dendritic cells (DCs) offers the advantage of triggering specific
signaling pathways to induce a tailored and robust immune
response. In this work, we describe a novel approach to targeted
antigen delivery by decorating the surface of polyanhydride
nanoparticles with specific carbohydrates to provide “pathogenlike”
properties that ensure nanoparticles engage C-type lectin
receptors on DCs. The surface of polyanhydride nanoparticles
was functionalized by covalent linkage of dimannose and lactose
residues using an amine carboxylic acid coupling reaction.
Coculture of functionalized nanoparticles with bone marrow derived
DCs significantly increased cell surface expression of
MHC II, the T cell costimulatory molecules CD86 and CD40,
the C-type lectin receptor CIRE and the mannose receptor
CD206 over the nonfunctionalized nanoparticles. Both nonfunctionalized
and functionalized nanoparticles were efficiently
internalized by DCs, indicating that internalization of functionalized
nanoparticles was necessary but not sufficient to activate
DCs. Blocking the mannose and CIRE receptors prior to the
addition of functionalized nanoparticles to the culture inhibited the increased surface expression of MHC II, CD40 and CD86.
Together, these data indicate that engagement of CIRE and the mannose receptor is a key mechanism by which functionalized
nanoparticles activate DCs. These studies provide valuable insights into the rational design of targeted nanovaccine platforms to
induce robust immune responses and improve vaccine efficacy.
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