Stabilization and bioactivity enhancement of epigallocatechin-3-O-gallate through poly(ethylene glycol) conjugation

Epigallocatechin-3- O -gallate (EGCG), the principal bioactive component of green tea, exhibits diverse biological activities, particularly antioxidant effects that contribute to its therapeutic potential. However, EGCG undergoes autoxidation under physiological conditions, leading to the formation of reactive oxygen species (ROS) and decomposition. This process results in poor chemical stability, limited bioavailability and potential cytotoxicity, thereby limiting its biomedical utility. To overcome these drawbacks, herein, EGCG was covalently conjugated to poly(ethylene glycol) (PEG), a hydrophilic and biocompatible polymer. The resulting conjugate (PEG–EGCG) effectively suppressed autoxidation and ROS formation, while enhancing cytocompatibility compared to native EGCG. Moreover, the conjugates spontaneously self-assembled into nanomicelles in aqueous environments, which may contribute to improved physicochemical stability. Importantly, PEG–EGCG maintained effective radical-scavenging activity in both acellular and cellular systems, supporting preservation of its antioxidant functionality. These findings highlight PEG conjugation as a promising strategy to stabilize EGCG and improve its biological performance for antioxidant-related biomedical applications. • EGCG was conjugated to PEG, preserving phenolic hydroxyl groups for bioactivities. • PEG conjugation enabled spontaneous self-assembly into nanomicelles. • PEG–EGCG suppressed autoxidation-associated ROS generation and cytotoxicity. • PEG–EGCG preserved antioxidant properties in both acellular and cellular systems.