Folic Acid Modified Poly(lactide-co-glycolide) Nanoparticles, Layer-by-Layer Surface Engineered for Targeted Delivery

The layer-by-layer (LbL) assembly technique was applied for the surface modification of biodegradable poly(lactide-co-glycolide) nanoparticles (NPs), employing poly(acrylic acid) (PAA), and polyethylenimine (PEI) as building blocks. Amino terminated poly(ethylene glycol) (PEG) and folate decorated PEG (PEG-FA) were grafted onto the multilayers via condensation between carboxylic groups and amine groups from PEG or PEG-FA. The LbL assembly and the covalent functionalization were monitored by means of zeta-potential measurements and the quartz crystal microbalance with dissipation technique (QCM-D). Protein adsorption after incubation of the NPs in culture medium containing optionally the serum proteins was investigated and related to cellular uptake. Experiments on cellular uptake showed that after PEGylation the uptake ratio of the NPs decreased significantly, but became three times larger when PEG-FA was grafted on the NPs instead of the PEG.