3174 - Proton-Induced Radiodynamic Therapy Based on PEG-Modified Nano-ZnO Composites and Mechanism of Action
Presenter(s)
G. Zhao1, X. Wang2, M. Liu3, and J. Wu2; 1Sichuan Cancer Hospital and Research Institute, Chengdu, China, 2Sichuan Cancer Hospital and Research Institute, University of Electronic Science and Technology of China, Chengdu, China, 3Sichuan Cancer Hospital and Research Institute University of Electronic Sciences and Technology of China, Radiation Oncology Department, Chengdu, China
Purpose/Objective(s): Proton-induced radiodynamic therapy (P-RDT) combines the advantages of proton therapy and photodynamic therapy, and which core is to achieve radiodynamic therapy by activating photosensitizers with high-energy protons to produce reactive oxygen (ROS). The "Bragg peak" characteristics of protons can not only reduce the radiation dose to endangered organs, but also achieve targeted activation of photosensitizers in tumor tissues, reduce the toxicity of photosensitizers to normal tissues behind the tumor, and synergistically enhance the protective effect on normal tissues. Traditional photosensitizers are generally organic nanomaterials with poor radiation resistance and are not suitable for high-energy proton irradiation. We hypothesize that PEG-modified Nano ZnO (PEG@ZnO NPs) composites can be used for P-RDT and enhance the biological effects of proton therapy.
Materials/Methods: PEG@ZnO NPs composites were constructed by modifying the surface of Nano ZnO particles with a diameter of 30 nm with PEG through esterification reaction. Several liver tumor cell comparison groups were set up, including control group: cells without any treatment, proton therapy group: only proton therapy, PEG@ZnO NPs group: only PEG@ZnO NPs were added, and P-RDT group: proton irradiation and PEG@ZnO NPs were added. Each comparison group received 2 Gy, 4 Gy and 6 Gy of proton irradiation, respectively. Fluorescence probe characterization and a cell counting kit method were used to detect the differences in ROS types, yields and tumor cell viability in each comparison group after irradiation.
Results: For ROS types and yields, there were significant differences among the comparison groups. Except for the control group, all other groups produced ROS to varying degrees. Among them, liver tumor cells produced the most -OH, O2- and 1O2 under treated by P-RDT, and the ROS yield was 70%, which was 92% higher than that of cells treated with proton therapy. For tumor cell viability, the viability of liver tumor cells treated with P-RDT was only 20% at 2 Gy, and with the increase of proton therapy dose, the viability further decreased, and the viability of tumor cells was only 5% at 6 Gy.
Conclusion: P-RDT based on PEG@ZnO NPs has obvious advantages in ROS generation and tumor cell viability. This technology is expected to enhance the biological effect of proton therapy, maximize the protection of normal tissues around tumors, and further optimize the biological dose distribution, achieving new breakthroughs in advanced radiotherapy technology.