Enhanced Hydrophilicity and Antifouling Performance of PEG with Sulfoxide-Containing Side Chains for Nanomedicine Applications

Poly(ethylene) glycol (PEG) has been widely used as an antifouling coating material for nanomedicines to improve their stability and safety. However, a growing number of studies have indicated that PEG is immunogenic and can cause unwanted immune responses, highlighting the need to develop alternative antifouling polymers for applications in nanomedicine. In this study, we report an innovative polymer, poly(2-(methylsulfinyl)ethyl glycidyl ether) (PMSOEGE), composed of a PEG backbone structure with sulfoxide-containing side chains. We demonstrated that PMSOEGE is highly biocompatible and more hydrophilic than conventional PEG due to the presence of highly polar and hydrophilic sulfoxide structures. Furthermore, PMSOEGE exhibits a much lower association with anti-PEG antibodies, as confirmed by an in vitro competitive enzyme-linked immunosorbent assay (ELISA). We applied PMSOEGE as a coating material for iron oxide nanoparticles (IONPs) and demonstrated that the PMSOEGE-coated IONPs showed significantly lower cellular uptake by macrophages compared with PEGylated IONPs. Protein corona analysis indicated that fewer proteins were associated with IONP@PMSOEGE. The results highlight the superior antifouling properties of PMSOEGE and highlight its potential to serve as a PEG alternative for various biological applications.