Zwitterionic Spherical Brush Loaded with Epigallocatechin-3-gallate Inhibits Protein Adsorption and Enhances Anti-Cancer Efficacy

Nanoparticle-based delivery systems for epigallocatechin-3-gallate (EGCG) have been developed to improve its bioavailability and anticancer performance. However, interactions between nanoparticles and nonspecific protein in biological fluids often compromise drug delivery efficacy. To address these, we here introduce zwitterionic poly(sulfobetaine methacrylate) (PSBMA) brushes onto the nanocarrier to inhibit protein adsorption. The resulting PSBMA-grafted gelatin nanoparticles (Gel-PSBMA) exhibited colloidal stability over half a month and antiabsorption exposing to bovine serum albumin (BSA) and fetal bovine serum (FBS). Meanwhile, the PSBMA brush grafting strategy increased EGCG loading capacity, enabled sustained release under both physiological (pH 7.4) and tumor microenvironment conditions (pH 6.5), and retained effective antioxidant activity. Furthermore, in vitro studies showed that EGCG-loaded Gel-PSBMA nanoparticles (Gel-PSBMA@EGCG) enhanced cytotoxicity against HeLa cells, compared with free EGCG. These results suggest that zwitterionic brush-modified nanoparticles offer an effective platform for optimizing polyphenolic compound delivery.