Introducing Sulfur Ylides as Charge-Neutral Termini for Mitigating Poly(ethylene glycol) Antigenicity in Nanomedicine.

ABSTRACT: The widespread use of polyethylene glycol (PEG) in biomedical applications has led to the emergence of anti-PEG antibodies, which accelerate systemic clearance and undermine the performance of PEGylated systems, including those of nanomedicines. Antibody recognition often involves the hydrophobic PEG terminus, highlighting the need for alternative end-functionalization strategies that enhance hydrophilicity while maintaining stealth properties. Here, we introduce a novel PEGylation concept using sulfur ylides bearing tri- and pentapeptides as terminal modifications. These ylide-PEG (yPEG) conjugates were integrated into polymeric nanoparticles as a model system, demonstrating that ylide functionalization maintains key physicochemical properties, such as ζ-potential and antifouling behavior

SUBMITTER: Sanchez-Cerrillo DM 

PROVIDER: S-EPMC12457994 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature