Jackson Nolan, Alhussan Abdulaziz, Bromma Kyle, Jay David, Donnelly James C, West Frederick G, Lavasanifar Afsaneh, Weinfeld Michael, Beckham Wayne, Chithrani Devika B
Department of Physics and Astronomy, University of Victoria, Victoria, BC V8P 5C2, Canada.
Department of Oncology, Division of Experimental Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
Pharmaceutics. 2022 Dec 14;14(12):2795. doi: 10.3390/pharmaceutics14122795.
Radiation therapy (RT) is frequently used to locally treat tumors. One of the major issues in RT is normal tissue toxicity; thus, it is necessary to limit dose escalation for enhanced local control in patients that have locally advanced tumors. Integrating radiosensitizing agents such as gold nanoparticles (GNPs) into RT has been shown to greatly increase the cure rate of solid tumors. The objective of this study was to explore the repurposing of an antimalarial drug, pyronaridine (PYD), as a DNA repair inhibitor to further enhance RT/GNP-induced DNA damage in cancerous cell lines. We were able to achieve inhibitory effects of DNA repair due to PYD at 500 nM concentration. Our results show a significant enhancement in DNA double-strand breaks of 42% in HeLa cells treated with PYD/GNP/RT in comparison to GNP/RT alone when irradiated with a dose of 2 Gy. Furthermore, there was a significant reduction in cellular proliferation for both HeLa and HCT-116 irradiated cells with the combined treatment of PYD/GNP/RT. Therefore, the emergence of promising novel concepts introduced in this study could lay the foundation for the transition of this treatment modality into clinical environments.
放射治疗（RT）常用于局部治疗肿瘤。放射治疗的主要问题之一是正常组织毒性；因此，对于局部晚期肿瘤患者，有必要限制剂量递增以加强局部控制。将诸如金纳米颗粒（GNP）等放射增敏剂整合到放射治疗中已被证明可大大提高实体瘤的治愈率。本研究的目的是探索将抗疟药物咯萘啶（PYD）重新用作DNA修复抑制剂，以进一步增强放射治疗/金纳米颗粒诱导的癌细胞系中的DNA损伤。我们能够在500 nM浓度下实现咯萘啶对DNA修复的抑制作用。我们的结果表明，当用2 Gy剂量照射时，与单独的金纳米颗粒/放射治疗相比，用咯萘啶/金纳米颗粒/放射治疗处理的HeLa细胞中DNA双链断裂显著增强了42%。此外，联合使用咯萘啶/金纳米颗粒/放射治疗时，HeLa和HCT-116照射细胞的细胞增殖均显著降低。因此，本研究中引入的有前景的新概念的出现可为这种治疗方式向临床环境的转变奠定基础。
