(Bio)degradable Materials


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

E. Steiert, J. Ewald, A. Wagner, U. A. Hellmich, H. Frey, P. R. Wich, Polym. Chem. 2020, 11, 551-559.

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.

M. Worm, D. Leibig, C. Dingels, H. Frey ACS Macro Lett., 2016, 5, 1357−1363.

Polyethylene glycol (PEG) has been used for decades to improve the pharmacokinetic properties of protein drugs, and several PEG-protein conjugates are approved by the FDA. However, the nondegradability of PEG restricts its use to a limiting molecular weight to permit renal excretion. In this work, we introduce a simple strategy to overcome the nondegradability of PEG by incorporating multiple pH-sensitive vinyl ether moieties into the polyether backbone. Copolymerization of 3,4-epoxy-1-butene (EPB) with ethylene oxide via anionic ring-opening polymerization (AROP) provides access to allyl moieties that can be isomerized to pH-cleavable propenyl units (isoEPB). The presence of a defined hydroxyl end group permits attachment to other functional molecules. The novel pH-degradable PEGs combine various desirable properties such as excellent long-term storage stability and cleavage in a physiologically relevant pH-range that render them promising candidates for biomedical application.