Prevention of Protein Adsorption and Macrophage Phagocytosis of Perfluorocarbon-Based Microsized Core-Shell Artificial Oxygen Carriers by Facile PEG Coatings

Polyethylene glycol (PEG)-coated microsized artificial oxygen carriers (AOCs) with a perfluorooctyl bromide (PFOB) core and poly(lactide-co-caprolactone) (PLC) shell were successfully fabricated using Shirasu porous glass (SPG) membrane emulsification. The PEG coating was achieved by adding the polylactide-b-polyethylene glycol-b-polylactide (PLA-PEG-PLA) block copolymer to the disperse phase during the SPG membrane emulsification process. During the DCM evaporation process, the three-layer structure of the PEG layer, PLC shell, and PFOB core of the AOCs spontaneously formed by phase separation. By adjustment of the ratio of PLA to PLA-PEG-PLA, the PEG chain density on the AOC surface was controlled and estimated as 0.1-2.4 chains nm-2 based on quantitative proton nuclear magnetic resonance analysis. It was expected that a loop PEG brush structure was formed on the surface of the AOCs owing to the ABA block copolymer structure of PLA-PEG-PLA. With the increase in PEG chain density, nonspecific adsorption of bovine serum albumin, gamma-globulin, and fibrinogen to AOCs decreased drastically and reached below 10 mu g cm-2. Additionally, phagocytosis of the AOCs, evaluated using the macrophage cell line RAW 264.7, was effectively prevented and the phagocytosis index decreased from 2 to almost 0. Finally, the PEG-coated core-shell AOCs exhibited excellent higher cell viability to RAW 264.7 than bare AOCs and showed oxygen delivery to hypoxia-responsive HeLa cells. Effective facile PEG coating on PFOB/PLC core-shell AOCs was successfully achieved simultaneously with membrane emulsification and subsequent evaporation-induced phase separation. It will be an effective strategy for membrane emulsification technology as well as the preparation of AOCs.