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 (PAATiOx) 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 PAATiOx 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 (p < 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.
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