Robust Proteinosomes with PEG Protein Mixed Corona for Enhanced Protection against Extreme pH Conditions and Trypsin Digestion

The wide applications of proteinosomes as protocells and nanoreactors benefit from their capsule-like structures and protein functions. In regular proteinosomes, the hydrophilic protein corona can be denatured in unfavorable conditions, such as extreme pH and protease. Herein, proteinosomes with a PEG protein mixed corona are prepared to protect the protein’s biofunction. The block copolymer polyethylene glycol-block-poly(di(ethylene glycol) methyl ether methacrylate) (PEG- b -PDEGMA) bearing an adamantyl group at the junction undergoes molecular recognition with β-cyclodextrin-modified proteins, affording miktoarm polymer–protein conjugates. β-Galactosidase (β-gal) and glucose oxidase (GO x ) were chosen as model proteins. Conjugates PEG- b -PDEGMA/β-gal, PEG- b -PDEGMA/GO x, and their mixture (PEG- b -PDEGMA/β-gal/GO x ) self-assembled into proteinosomes consisting of a PDEGMA membrane and a PEG protein mixed corona at temperatures above their lower critical solution temperatures. The activities of enzymes in all the proteinosomes were well preserved, and the mixed corona proteinosomes exhibited more effective protection against extreme pH conditions and trypsin digestion than the regular ones.