Gold-Nanoparticles-Enhanced Production of Reactive Oxygen Species in Cells at Spread-Out Bragg Peak under Proton Beam Radiation

Chang-Yun Lo; Shiao-Wen Tsai; Huan Niu; Fang-Hsin Chen; Hsiao-Chien Hwang; Tsi-Chian Chao; Ing-Tsung Hsiao; Jiunn-Woei Liaw

doi:10.1021/acsomega.3c01025

Gold-Nanoparticles-Enhanced Production of Reactive Oxygen Species in Cells at Spread-Out Bragg Peak under Proton Beam Radiation

ACS Omega. 2023 May 9;8(20):17922-17931. doi: 10.1021/acsomega.3c01025. eCollection 2023 May 23.

Authors

Chang-Yun Lo¹, Shiao-Wen Tsai^{2

3}, Huan Niu⁴, Fang-Hsin Chen^{5

6

7}, Hsiao-Chien Hwang⁸, Tsi-Chian Chao⁷, Ing-Tsung Hsiao⁷, Jiunn-Woei Liaw^{1

8

9}

Affiliations

¹ Department of Mechanical Engineering, Chang Gung University, Taoyuan 333, Taiwan.
² Department of Biomedical Engineering, Chang Gung University, Taoyuan 333, Taiwan.
³ Department of Periodontics, Chang Gung Memorial Hospital, Taipei 105, Taiwan.
⁴ Accelerator Laboratory, Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 300, Taiwan.
⁵ Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 300, Taiwan.
⁶ Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
⁷ Department of Medical Imaging and Radiological Science, Chang Gung University, Taoyuan 333, Taiwan.
⁸ Proton and Radiation Therapy Center, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
⁹ Department of Mechanical Engineering, Ming Chi University of Technology, New Taipei City 243, Taiwan.

Abstract

This study investigates the radiobiological effects of gold nanoparticles (GNPs) as radiosensitizers for proton beam therapy (PBT). Specifically, we explore the enhanced production of reactive oxygen species (ROS) in GNP-loaded tumor cells irradiated by a 230 MeV proton beam in a spread-out Bragg peak (SOBP) zone obtained by a passive scattering system. Our findings indicate that the radiosensitization enhancement factor is 1.24 at 30% cell survival fraction, 8 days after 6 Gy proton beam irradiation. Since protons deposit the majority of their energy at the SOBP region and interact with GNPs to induce more ejected electrons from the high-Z GNPs, these ejected electrons then react with water molecules to produce excessive ROS that can damage cellular organelles. Laser scanning confocal microscopy reveals the excessive ROS induced inside the GNP-loaded cells immediately after proton irradiation. Furthermore, the damage to cytoskeletons and mitochondrial dysfunction in GNP-loaded cells caused by the induced ROS becomes significantly severe, 48 h after proton irradiation. Our biological evidence suggests that the cytotoxicity of GNP-enhanced ROS production has the potential to increase the tumoricidal efficacy of PBT.