Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX. The introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions. Incorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings.

中文翻译：

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通过纳米颗粒和化疗双重增强前列腺癌的放射敏感性

放射治疗 (RT) 是许多癌症患者治疗方案中的重要组成部分。然而，由于诱导的正常组织毒性，改善疗效所需的剂量递增受到阻碍。在 RT 治疗中引入放射增敏剂是目前正在探索解决这一问题的一种途径。通过将放射增敏剂引入肿瘤部位，可以优先增强局部沉积剂量。金纳米粒子 (GNP) 是一种潜在的候选者，它在通过增强 DNA 损伤来提高癌细胞的放射敏感性方面表现出了巨大的希望。此外，多西他赛 (DTX) 是一种化疗药物，可将细胞阻滞在细胞周期的 G2/M 期，该期对辐射损伤最敏感。我们假设，通过将 DTX 纳入 GNP 增强放射治疗中，我们可以进一步改善癌细胞的放射增敏作用。为了评估这一策略，我们分析了体外单层细胞培养物以及体内小鼠前列腺异种移植模型的放射治疗效果，同时使用临床上可行的 GNP 和 DTX 浓度。将 DTX 引入 GNP 增强放射治疗进一步增强了癌细胞的放射治疗效果。给予 2 Gy 剂量后，与单独使用 GNP 相比，GNP/DTX 组合的 DNA 双链断裂增加了 38%。体内结果显示，与给予小鼠单次 5 Gy 剂量后的 GNP/RT 相比，在 30 天的观察期内，GNP/DTX/RT 治疗的肿瘤生长显着减少。该治疗策略还使小鼠 100% 存活，这是其他治疗条件下未观察到的。将 DTX 与 GNP 和 RT 结合起来可以提高 RT 治疗的疗效。我们的研究表明，治疗策略可以通过局部剂量增加来改善肿瘤控制。由于本研究中使用的浓度在临床上可行，因此该策略有可能转化为临床环境。