Targeting of sialoadhesin-expressing macrophages through antibody-conjugated (polyethylene glycol) poly(lactic-co-glycolic acid) nanoparticles

Abstract

This research aims to evaluate different-sized nanoparticles consisting of (polyethylene glycol) (PEG) poly(lactic-co-glycolic acid) (PLGA), loaded with fluorescein isothiocyanate for nanoparticle uptake and intracellular fate in sialoadhesin-expressing macrophages, while being functionalized with anti-sialoadhesin antibody. Sialoadhesin is a macrophage-restricted receptor, expressed on certain populations of resident tissue macrophages, yet is also upregulated in some inflammatory conditions. The nanocarriers were characterized for nanoparticle size (84–319 nm), zeta potential, encapsulation efficiency, and in vitro dye release. Small (86 nm) antibody-functionalized PEG PLGA nanoparticles showed persisting benefit from sialoadhesin-targeting after 24 h compared to the control groups. For small (105 nm) PLGA nanoparticles, uptake rate was higher for antibody-conjugated nanoparticles, though the total amount of uptake was not enhanced after 24 h. For both plain and functionalized small-sized (PEG) PLGA nanoparticles, no co-localization between nanoparticles and (early/late) endosomes nor lysosomes could be observed after 1-, 4-, or 24-h incubation time. In conclusion, decorating (PEG) PLGA nanocarriers with anti-sialoadhesin antibodies positively impacts macrophage targeting, though it was found to be formulation-specific.