Controlling the morphology of glyco-nanoparticles in water using block copolymer mixtures: the effect on cellular uptake

Poly[(2-(alpha-D-mannosyloxy)ethyl acrylate)-block-(n-butyl acrylate)], P(ManA-b-BA), and poly[poly(ethylene glycol) methyl ether acrylate]-block-(n-butyl acrylate), P(OEGMEA-b-BA), diblock copolymers were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The binary mixtures of P(ManA-b-BA)/P(OEGMEA-b-BA) diblock copolymers were self-assembled in aqueous solution at different compositions and various morphologies were obtained by a nanoprecipitation process. Characterization of the particle morphology was carried out by dynamic light scattering (DLS) evidencing nanoparticles with different morphologies and narrow size distributions. Nanostructure details were also observed by using transmission electron microscopy (TEM) and were in good agreement with light scattering measurements showing the assembly of core-shell, micelle, rod-like, kiwifruit-like and onion-like morphologies, and the particle morphology varying with the mixing ratio of the diblock copolymers. Cellular uptake by macrophages, which was investigated using confocal laser scanning microscopy (CLSM) and flow cytometry, revealed that the amount of uptake is predominantly dependent on the mannose concentration and not on the shape or size of the nanoparticles.