Hidden hydrophobicity impacts polymer immunogenicity. Issue 8 (30th January 2023)

• Record Type: Journal Article
• Authors: Yuan, Zhefan; McMullen, Patrick; Luozhong, Sijin; Sarker, Pranab; Tang, Chenjue; Wei, Tao; Jiang, Shaoyi
• Is Part Of: Chemical science. Volume 14:Issue 8(2023)
• Page Start: 2033
• Page End: 2039
• Publication Date: 2023-01-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2sc07047b
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : The hidden hydrophobicity of conventional polymers widely considered as hydrophilic is closely related to their immunogenicity when they are conjugated to immunogenic proteins. Abstract : Antibodies against poly(ethylene glycol) (PEG) have been found to be the culprit of side reactions and efficacy loss of a number of PEGylated drugs. Fundamental mechanisms of PEG immunogenicity and design principles for PEG alternatives still have not been fully explored. By using hydrophobic interaction chromatography (HIC) under varied salt conditions, we reveal the "hidden" hydrophobicity of those polymers which are generally considered as hydrophilic. A correlation between the hidden hydrophobicity of a polymer and its polymer immunogenicity is observed when this polymer is conjugated with an immunogenic protein. Such a correlation of hidden hydrophobicity vs. immunogenicity for a polymer also applies to corresponding polymer–protein conjugates. Atomistic molecular dynamics (MD) simulation results show a similar trend. Based on polyzwitterion modification and with this HIC technique, we are able to produce extremely low-immunogenic protein conjugates as their hydrophilicity is pushed to the limit and their hydrophobicity is eliminated, breaking the current barriers of eliminating anti-drug and anti-polymer antibodies.