胰腺癌是最致命的癌症之一，现有的治疗方法不足以提供足够的疗效。迫切需要新颖和更有效的治疗方法来解决这一严重的医学挑战。本研究旨在评估纳米金颗粒（GNPs）与放射疗法（RT）联合应用对癌症的抗癌疗效。采用MIA PaCa-2癌细胞和患者来源的与癌相关纤维母细胞（CAF-98）的三维胰腺癌共培养球模型。球体经过GNPs（7.5 μg/mL）和2 Gy的RT处理。通过CellTiter-Glo 3D试验评估球体的细胞存活率，并通过53BP1这一DNA损伤标志物的表达使用免疫荧光试验评估DNA双链断裂（DSBs）情况。与单养样本相比，共培养样本显示了10.8%（p < 0.05）的增殖和13.0%（p < 0.05）的DNA DSB降低。然而，与单养球体相比，共培养样本中GNPs的摄取增加了175%（p < 0.001）。使用GNPs/RT，我们能够显示球体大小显著减小了6.2%（p < 0.05），共培养样本的DNA DSB损伤增加了14.3%（p < 0.05）。 GNPs与RT的组合展示了显著的放射增敏效应，为增强癌症治疗疗效提供了有希望的方法。这些效应在更耐药的共培养球体模型中尤为引人注目。

Pancreatic cancer stands among the deadliest forms of cancer, and the existing treatments fall short of providing adequate efficacy. Novel and more effective treatment approaches are urgently required to address this critical medical challenge. In this study, we aimed to evaluate the anti-cancer efficacy of gold nanoparticles (GNPs) in combination with radiotherapy (RT). A 3D pancreatic cancer co-culture spheroid model of MIA PaCa-2 cancer cells and patient-derived cancer-associated fibroblasts (CAF-98) was used. The spheroids were treated with GNPs (7.5 μg/mL) and 2 Gy of RT. The spheroids' cell viability was assessed through the CellTiter-Glo 3D assay, and an immunofluorescence assay was used to assess the DNA DSBs via the expression of the DNA damage marker 53BP1. Co-culture samples showed a 10.8% (p < 0.05) increase in proliferation and a 13.0% (p < 0.05) decrease in DNA DSB when compared to monoculture samples, However, they displayed a 175% (p < 0.001) increase in GNPs uptake when compared to monoculture spheroids. Using GNPs/RT, we were able to show a significant reduction of 6.2% (p < 0.05) in spheroid size and an increase of 14.3% (p < 0.05) in DNA DSB damage in co-culture samples. The combination of GNPs with RT demonstrated remarkable radiosensitization effects, representing a promising approach to enhance cancer treatment efficacy. These effects were particularly noteworthy in the more treatment-resistant co-culture spheroid model.