Synthesis of Antifouling Poly(ethylene glycol) Brushes via “Grafting to” Approach for Improved Biodistribution

Polyethylene glycol (PEG) modification of materials has been identified to mitigate the challenge of biofouling. However, the practical application of PEGylation has been hampered by a low PEGylation density on the material surface. Therefore, developing efficient strategies to promote the PEGylation density is crucial. In this study, PEG brushes (PBs) with various structures were synthesized and their physicochemical properties and biomedical applications were investigated. Compared to benzaldehyde (BA), <i>o</i>-phthalaldehyde (OPA) exhibited higher reactivity with amine groups, resulting in increased grafting density (as high as 96.3%) and improved antifouling properties of PEG brushes. Bottlebrushes fabricated by PEG-OPA and polylysine demonstrated a prolonged circulation time in blood and enhanced potential for magnetic resonance imaging of tumors. Furthermore, the rigidity of the backbone was found to be crucial for the antifouling properties of PEG brushes both <i>in vitro</i> and <i>in vivo</i>. These findings are significant and provide valuable insights into designing biomaterials with superior antifouling performance.