Effects of Au States in Thiol-Organosilica Nanoparticles on Enzyme-like Activity for X-ray Sensitizer Application: Focus on Reactive Oxygen Species Generation in Radiotherapy.

Abstract

In radiotherapy, the use of Au nanoparticles (Au NPs) has been proposed to enhance cell damage by X-ray irradiation. Although the role of Au in radiotherapy is not fully understood, the catalytic activity of Au has been actively studied in the industrial field. Moreover, owing to their enzyme-like activity and high biocompatibility in vitro and in vivo, Au NPs present significant potential for biological applications. In this study, we incorporated different Au states both on the surface and embedded in thiol-organosilica (thiol-OS/Au series) to investigate the efficiency of anticancer cell activity of Au in radiotherapy. The thiol-OS/Au series comprised different Au(I)/Au(0) ratios and Au NPs, and different sizes of Au NPs were embedded in thiol-OS/Au. These thiol-OS/Au series samples were evaluated for enzyme-like activities in reactive oxygen species (ROS) generation by X-ray irradiation. Thiol-OS/Au embedded with small Au NPs (AC600/thiol-OS/Au) exhibited peroxidase (POD)-like activity under acidic conditions. This POD-like activity improved ROS generation and cytotoxicity under X-ray irradiation. Furthermore, AC600/thiol-OS/Au exhibited catalase (CAT)-like activity under basic conditions and showed no cytotoxicity toward nonirradiated cells. These results revealed the efficiency of functionalizing with small Au NPs that possess pH-controlled POD- and CAT-like activity as a radiosensitizer. We compared the suitability of using Au with different states to obtain the thiol-OS/Au series samples for application as radiosensitizers. The findings of this study will aid the design of efficacious strategies for the Au nanostructure-based radiotherapy of cancer cells.