Competition of PEG coverage density and con-A recognition in mannose/PEG bearing nanoparticles

Cell specific ligand molecules are attached to polyethylene glycol (PEG) modified nanoparticles to enhance the drug delivery efficiency. The tethered PEG would interfere in ligand recognition as well as providing biocompatibility to the nanoparticles. The denser PEG can give the greater biocompatibility, while should more hamper the ligand recognition. Therefor it is important to tune PEG density at an appropriate amount to compensate these two factors. In this study, we prepared a series of nanoparticles composed of α-mannose-bearing lipid, dioleoyltrimethyl ammoniumpropane (DOTAP) and 1,2-distearoyl-sn-glycero -3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). The nanoparticles were characterized with dynamic light scattering (DLS), field flow fractionation (FFF), small angle X-ray scattering (SAXS), and quartz-crystal microbalance (QCM). Based on the structural parameter obtained from DLS, SAXS, and FFF, we determined the PEG crowding parameter (σ) quantitatively; when σ=1.0, the PEG chain occupies the same value on the surface as when the chain is present in the unperturbed state, and at σ=1.0, the PEG chains start to contact each other. We found that the recognition ability had the maximum around σ∼0.75 and there was the critical composition at σ=1.0 for which the recognition was drastically reduced. The present results demonstrated that quantitative characterization and controlling the PEG density are key to designing effective targeting delivery system.