Prevention\nof Protein\nAdsorption and Macrophage Phagocytosis\nof Perfluorocarbon-Based Microsized Core–Shell Artificial Oxygen\nCarriers by Facile PEG Coatings

Polyethylene\nglycol (PEG)-coated microsized artificial\noxygen carriers\n(AOCs) with a perfluorooctyl bromide (PFOB) core and poly(lactide-<i>co</i>-caprolactone) (PLC) shell were successfully fabricated\nusing Shirasu porous glass (SPG) membrane emulsification. The PEG\ncoating was achieved by adding the polylactide-<i>b</i>-polyethylene\nglycol-<i>b</i>-polylactide (PLA–PEG–PLA)\nblock copolymer to the disperse phase during the SPG membrane emulsification\nprocess. During the DCM evaporation process, the three-layer structure\nof the PEG layer, PLC shell, and PFOB core of the AOCs spontaneously\nformed by phase separation. By adjustment of the ratio of PLA to PLA–PEG–PLA,\nthe PEG chain density on the AOC surface was controlled and estimated\nas 0.1–2.4 chains nm<sup>–2</sup> based on quantitative\nproton nuclear magnetic resonance analysis. It was expected that a\nloop PEG brush structure was formed on the surface of the AOCs owing\nto the ABA block copolymer structure of PLA–PEG–PLA.\nWith the increase in PEG chain density, nonspecific adsorption of\nbovine serum albumin, γ-globulin, and fibrinogen to AOCs decreased\ndrastically and reached below 10 μg cm<sup>–2</sup>.\nAdditionally, phagocytosis of the AOCs, evaluated using the macrophage\ncell line RAW 264.7, was effectively prevented and the phagocytosis\nindex decreased from 2 to almost 0. Finally, the PEG-coated core–shell\nAOCs exhibited excellent higher cell viability to RAW 264.7 than bare\nAOCs and showed oxygen delivery to hypoxia-responsive HeLa cells.\nEffective facile PEG coating on PFOB/PLC core–shell AOCs was\nsuccessfully achieved simultaneously with membrane emulsification\nand subsequent evaporation-induced phase separation. It will be an\neffective strategy for membrane emulsification technology as well\nas the preparation of AOCs.