| Summary: | Titanium dioxide nanoparticles (TiO<sub>2</sub> 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 TiO<sub>2</sub> NPs have a low cellular uptake and can induce cell proliferation. This suggests that TiO<sub>2</sub> 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 TiO<sub>2</sub> NPs (EGF-TiO<sub>2</sub> PEG NPs). In this work, we studied the effect of EGF conjugation on the cellular uptake of TiO<sub>2</sub> PEG NPs. Then, we investigated the effect of both non-conjugated and EGF-TiO<sub>2</sub> PEG NPs on the A431 epidermal cancer cell line, proliferation and growth via the investigation of EGFR localization and expression. Our results indicated that TiO<sub>2</sub> PEG NPs induced EGFRs aggregation on the A431 cells surface and induced cell proliferation. In addition, EGF-TiO<sub>2</sub> PEG NPs induced the internalization of EGFRs inside of cells with increased cellular NPs uptake and decreased cellular proliferation compared to TiO<sub>2</sub> PEG NPs-treated cells. These findings suggest that EGF conjugation can increase the efficacy of TiO<sub>2</sub> PEG NPs for biomedical applications such as PDD and PDT with decreased risk of tumor overgrowth.
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