EGF Conjugation Improves Safety and Uptake Efficacy of Titanium Dioxide Nanoparticles.

Basma Salama,Mohamed El-Adl,Gehad El-Sayed,Chia-Jung Chang,Akiyoshi Taniguchi,Koki Kanehira,El-Said El-Sherbini

doi:10.3390/molecules25194467

Basma Salama, Mohamed El-Adl + Show 5 more

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https://doi.org/10.3390/molecules25194467

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Abstract

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.

Highlights

Titanium dioxide nanoparticles (TiO2 NPs) have a high potential to be applied in nanomedicine based on their unique properties, including biocompatibility, photocatalytic activity, and light scattering properties [1,2]
TiO2 NPs can associate with hepatocyte growth factor receptors (HGFRs), leading to receptor aggregation, facilitating the recruitment of more signal transduction molecules, and HepG2 cell proliferation and growth [13]. These results suggest that TiO2 NPs can increase the risk of tumor overgrowth while being used for photodynamic diagnosis (PDD) and photodynamic therapy (PDT)
We evaluated the effect of EGF conjugation on the cellular uptake level of TiO2 PEG NPs

Summary

Introduction

Titanium dioxide nanoparticles (TiO2 NPs) have a high potential to be applied in nanomedicine based on their unique properties, including biocompatibility, photocatalytic activity, and light scattering properties [1,2]. TiO2 NPs have a potential in cancer therapy and bioimaging applications such as photodynamic therapy (PDT) and photodynamic diagnosis (PDD) [3,4]. In PDT, TiO2 NPs are used as a photosensitizer. TiO2 NPs generate reactive oxygen species (ROS) and induce cell death when activated by irradiation at an appropriate wavelength [5]. PDD is a very effective technique for cancer localization and intraoperative tumor visualization, and TiO2 NPs have been used to enhance its fluorescence signals [6,7]. Recent work has found that TiO2 NPs can decrease photobleaching and enhance and prolong fluorescent PDD agents, resulting in improved tumor visualization [8]. It has been recommended to combine PDT and PDD for the simultaneous treatment and detection

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