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

J Nanopart Res. 2022;24(3):65. doi: 10.1007/s11051-022-05451-1. Epub 2022 Mar 14.

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.

Keywords: Drug delivery; Macrophage; Nanoparticle; PEG PLGA; PLGA; Sialoadhesin; Targeting.