pH-Responsive protein nanoparticles via conjugation of degradable PEG to the surface of cytochrome c

Proteins represent a versatile biopolymer material for the preparation of nanoparticles. For drug delivery applications an acid-triggered disassembly and payload release is preferred. Herein, we present a protein nanoparticle system based on cytochrome c, which is surface-modified with acid-degradable polyethylene glycol (PEGylation). pH-Sensitivity was obtained through vinyl ether moieties distributed in the polyether backbone. When PEGylated, cytochrome c shows a different solubility behaviour in organic solvents, which allows for particle preparation using an emulsion-based solvent evaporation method. The resulting particles are stable under physiological conditions but degrade at acidic pH values. Fluorescence-labelled dextran was successfully encapsulated as a hydrophilic model payload in these degradable nanoparticles and a release under acidic conditions was observed.