Nanoparticles To Study Lectins in Caenorhabditis elegans: Multivalent Galactose β1-4 Fucose-Functionalized Dendrimers Provide Protection from Oxidative Stress

Abstract

Galectins are galactoside-binding lectins that are functional dimers or higher-order oligomers. Multivalent binding has been shown to augment the relatively low affinity of the galectins for their galactoside-binding partners, enabling the galectins to play an important role in the global remodeling of cells that occurs during the stress conditions of disease states, including heart disease and cancer. The presence of galectins in the nematode Caenorhabditis elegans and their galactoside-binding properties have been demonstrated, but the role of multivalent interactions for C. elegans galectins is unknown. Here, we describe the synthesis of Galβ1-4Fuc-functionalized poly(amidoamine) dendrimers and their utility in studies using C. elegans during oxidative stress. C. elegans were fed Galβ1-4Fuc-functionalized dendrimers and RNA interference to knock down lectins lec-1 and lec-10 while undergoing oxidative stress. C. elegans that were pretreated with the glycodendrimers were less susceptible to oxidative stress than untreated controls. Worms that were fed fluorescently tagged glycodendrimers and imaged indicated that the dendrimers are primarily present in the digestive tract of the worms, and uptake into the vulva and proximal gonads could also be observed in some instances. This study suggests that multivalently presented Galβ1-4Fuc can protect C. elegans from oxidative stress.