Therapeutic Efficacy of Carbon Ion Irradiation Enhanced by 11-MUA-Capped Gold Nanoparticles: An in vitro and in vivo Study

Abstract

Pengcheng Zhang,1– 4 Boyi Yu,1,2 Xiaodong Jin,1,2 Ting Zhao,1 Fei Ye,1,2 Xiongxiong Liu,1,2 Ping Li,1,2 Xiaogang Zheng,1 Weiqiang Chen,1,2 Qiang Li1,2 1Institute of Modern Physics, Chinese Academy of Sciences; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, 730000, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 3The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China; 4Department of Radiation Oncology, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of ChinaCorrespondence: Weiqiang Chen; Qiang LiInstitute of Modern Physics, Chinese Academy of Sciences; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Lanzhou, Gansu Province, 730000, People’s Republic of ChinaEmail [email protected]; [email protected]: Gold nanoparticles (AuNPs) are widely studied as radiosensitizers, but their radiosensitization in carbon ion radiotherapy is unsatisfactory. There is a lack of in vivo data on the radiosensitization of AuNPs under carbon ion irradiation. This study focused on the radiosensitization effect of AuNPs in the mouse melanoma cell line B16-F10 in vitro and in vivo.Materials and Methods: 11-mercaptoundecanoic acid (11-MUA)-coated gold (Au) nanoparticles (mAuNPs) formulations were prepared and characterized. To verify the radiosensitization effect of mAuNPs, hydroxyl radicals were generated in aqueous solution, and the detection of intracellular reactive oxygen species (ROS) and clone survival were carried out in vitro. The tumor growth rate (TGR) and survival of mice were analyzed to verify the radiosensitization effect of mAuNPs in vivo. The apoptosis of tumor cells was detected, and the expression of key proteins in the apoptosis pathway was verified by immunohistochemistry.Results: The intracellular ROS level in B16-F10 cells was enhanced by mAuNPs under carbon ion irradiation. The sensitization rate of mAuNPs was 1.22 with a 10% cell survival rate. Compared with irradiation alone, the inhibitory effect of mAuNPs combined with carbon ion irradiation on tumor growth was 1.94-fold higher, the survival time of mice was prolonged by 1.75-fold, and the number of apoptotic cells was increased by 1.43-fold. The ratio of key proteins Bax and Bcl2 in the apoptosis pathway was up-regulated, and the expression of caspase-3, a key executor of the apoptosis pathway, was up-regulated.Conclusion: In in vivo and in vitro experiments, mAuNPs showed radiosensitivity to carbon ion irradiation. The sensitization effect of mAuNPs on mice tumor may be achieved by activating the mitochondrial apoptosis pathway and increasing tumor tissue apoptosis. To our best knowledge, the present study is the first in vivo evidence for radiosensitization of mAuNPs in tumor-bearing mice exposed to carbon ion irradiation.Keywords: gold nanoparticles, radiosentization, carbon ion irradiation, tumor-bearing mice, apoptosis

Keywords

• gold nanoparticles
• radiosentization
• carbon ion irradiation
• tumor-bearing mice
• apoptosis