Cecchi Daniel, Jackson Nolan, Goharian Mehran, Beckham Wayne, Chithrani Devika
Department of Physics and Astronomy, University of Victoria, Victoria, British Columbia, Canada.
British Columbia Cancer, Victoria, British Columbia, Canada.
Med Phys. 2025 Jul;52(7):e18006. doi: 10.1002/mp.18006.
BACKGROUND: Radiation therapy is a pivotal part of the treatment plan for many cancer patients. Effective dose escalation in the tumour is required to achieve optimal curative results but is hindered by normal tissue toxicity. Gold nanoparticles (GNPs) as radiosensitizers to improve the radiation cross-section of malignant tissue is one avenue currently being explored to improve therapeutic results. It is hypothesized that at lower incident photon energies, dose enhancement from GNPs should be significantly greater compared to high-energy irradiations due to a greater photoelectric cross-section. PURPOSE: To assess GNP radiosensitization in vitro during low-energy, high-dose-rate brachytherapy (HDR-BT) irradiations and compare to the measured radiosensitization from a 6MV photon beam from a clinical linear accelerator (LINAC). METHODS: A novel Solid Water Phantom was developed for uniform irradiations from a common HDR-BT source (192-Ir) and verified using EBT-4 radiochromic film. HeLa (cervical) and PC3 (prostate) monolayer cell cultures were used to represent common HDR-BT treatment sites. The cells were dosed at 10 µg/mL concentration with functionalized 12 nm spherical GNPs. GNP uptake in the cellular membrane was quantified using live-cell imaging and a trace element analysis technique. Cell cultures with or without GNPs were irradiated from the 192-Ir source or clinical 6 MV photon beam from a LINAC to a 200 cGy dose prescription. Cellular viability was measured using a clonogenic assay and DNA double-strand break (DSB) assay. RESULTS: Endocytosis of spherical GNPs was confirmed 24 h post-incubation, resulting in an average of 8.7 × 10 GNPs/cell and 6.0 × 10 GNPs/cell for HeLa and PC3 cell cultures, respectively. The incorporation of GNPs induced 183% (p < 0.001) and 364% (p = 0.01) greater DNA DSBs with HDR-BT irradiations compared to LINAC irradiations for HeLa and PC3 cells, respectively, after the 200 cGy prescription. GNPs reduced the survival fraction of HeLa and PC3 cells after 2 weeks post-irradiation by 4.6% (p < 0.05) and 8.5% (p < 0.05), respectively, with HDR irradiations compared to LINAC irradiations. CONCLUSIONS: Our results suggest GNP incorporation into HDR-BT is a viable and effective treatment strategy. As our dosing concentration in this study induced no measurable cellular toxicity, this strategy has the potential to be implemented in clinical scenarios. Ultimately, we believe that incorporating GNPs into radiotherapy workflows can increase radiotherapeutic efficacy, improving the quality of life for cancer patients.
背景：放射治疗是许多癌症患者治疗方案的关键组成部分。为实现最佳治愈效果，需要在肿瘤中有效提高剂量，但这受到正常组织毒性的阻碍。金纳米颗粒（GNPs）作为放射增敏剂以改善恶性组织的辐射截面是目前正在探索的提高治疗效果的一条途径。据推测，在较低的入射光子能量下，由于更大的光电截面，与高能辐射相比，GNPs的剂量增强应该显著更大。 目的：评估在低能量、高剂量率近距离放射治疗（HDR - BT）照射期间GNPs的体外放射增敏作用，并与临床直线加速器（LINAC）的6MV光子束测得的放射增敏作用进行比较。 方法：开发了一种新型固体水模体，用于来自常见HDR - BT源（192 - Ir）的均匀照射，并使用EBT - 4放射变色胶片进行验证。使用HeLa（宫颈）和PC3（前列腺）单层细胞培养物来代表常见的HDR - BT治疗部位。细胞以10μg/mL的浓度用功能化的12nm球形GNPs给药。使用活细胞成像和微量元素分析技术对细胞膜中GNPs的摄取进行定量。对有或没有GNPs的细胞培养物，从192 - Ir源或LINAC的临床6MV光子束照射至200cGy的剂量处方。使用克隆形成试验和DNA双链断裂（DSB）试验测量细胞活力。 结果：孵育24小时后证实球形GNPs的内吞作用，HeLa和PC3细胞培养物中平均分别为8.7×10个GNPs/细胞和6.0×10个GNPs/细胞。在200cGy处方后，与LINAC照射相比，对于HeLa和PC3细胞，HDR - BT照射时GNPs的掺入分别诱导了多183%（p < 0.001）和364%（p = 0.01）的DNA DSBs。与LINAC照射相比，HDR照射后2周，GNPs分别使HeLa和PC3细胞的存活分数降低了4.6%（p < 0.05）和8.5%（p < 0.05）。 结论：我们的结果表明将GNPs掺入HDR - BT是一种可行且有效的治疗策略。由于我们在本研究中的给药浓度未诱导可测量的细胞毒性，该策略有可能在临床场景中实施。最终，我们相信将GNPs纳入放射治疗工作流程可以提高放射治疗效果，改善癌症患者的生活质量。
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