EGF Conjugation Improves Safety and Uptake Efficacy of Titanium Dioxide Nanoparticles

Titanium dioxide nanoparticles (TiO₂ NPs) have a strong potential for cancer therapeutic and bioimaging applications such as photodynamic therapy (PDT) and photodynamic diagnosis (PDD). Our previous results have shown that TiO₂ NPs have a low cellular uptake and can induce cell proliferation. This suggests that TiO₂ NPs could increase the risk of tumor overgrowth while being used for PDD and PDT. To solve this problem, we constructed epidermal growth factor-ligated polyethylene glycol-coated TiO₂ NPs (EGF-TiO₂ PEG NPs). In this work, we studied the effect of EGF conjugation on the cellular uptake of TiO₂ PEG NPs. Then, we investigated the effect of both non-conjugated and EGF-TiO₂ PEG NPs on the A431 epidermal cancer cell line, proliferation and growth via the investigation of EGFR localization and expression. Our results indicated that TiO₂ PEG NPs induced EGFRs aggregation on the A431 cells surface and induced cell proliferation. In addition, EGF-TiO₂ PEG NPs induced the internalization of EGFRs inside of cells with increased cellular NPs uptake and decreased cellular proliferation compared to TiO₂ PEG NPs-treated cells. These findings suggest that EGF conjugation can increase the efficacy of TiO₂ PEG NPs for biomedical applications such as PDD and PDT with decreased risk of tumor overgrowth.