Polyphenol-Mediated Antibody Functionalization of Titanium Peroxide Nanoparticles for Cancer Cell Targeting

Cell targeting would benefit various biotechnological applications such as disease diagnosis and cancer therapy. However, efficiently functionalizing nanoparticles with targeting ligands such as antibodies remains challenging. For example, poly(acrylic acid)-modified titanium peroxide NPs (PAATiO<i>x</i>) have shown promising radiosensitizing effects but suffer from poor tumor accumulation due to a lack of targeting. Herein, we developed a simple, one-pot process to noncovalently graft anti-CD44 antibodies onto the surface of PAATiO<i>x</i> NPs using tannic acid, a polyphenol that can bind to diverse surfaces and biomolecules via multiple molecular interactions. We evaluated the cellular binding, internalization, therapeutic efficacy, and biodistribution of the targeted particles. The antibody-functionalized NPs exhibited ∼2-fold enhanced binding to CD44-expressing cells compared to unmodified NPs and enhanced cellular internalization in vitro (2.4-fold in MIAPaCa-2 cells and 6.5-fold in MDA-MB-231 cells). Additionally, the NPs maintained their radiosensitizing property, significantly inhibiting the growth of CD44-expressing cells by 2-fold compared with CD44-negative cells. In vivo biodistribution studies revealed ∼2-fold greater tumor accumulation of the targeted NPs compared to unmodified NPs (<i>p</i> < 0.05). This polyphenol-mediated antibody coating strategy is a versatile and broadly applicable platform for enhancing nanoparticle delivery to specific cell populations, with potential for improving radiotherapy outcomes in CD44-positive tumors.