Aborig Mohamed, Alsefaou Moad, Osei Ernest, Wettig Shawn
School of Pharmacy, University of Waterloo Kitchener ON N2G 1C5 Canada
Schulich School of Medicine & Dentistry, Western University London N6A 5C1 Ontario Canada
Nanoscale Adv. 2025 Jul 10. doi: 10.1039/d5na00376h.
Prostate cancer remains a leading cause of cancer-related mortality in men, with the three main treatment modalities being surgery, chemotherapy, radiotherapy, or a combination depending on the stage. However, the use of radiotherapy is often restricted by dose-limiting toxicity of the organs at risk. To address this challenge, we developed curcumin-coated gold nanoparticles (Curc-GNPs) that leverage both the photoelectric properties of gold and the radiosensitizing effects of curcumin. In this study, we explore the stability, cytotoxicity, cellular uptake, and radio-sensitizing potential of Curc-GNP in PC-3 prostate cancer cells. Curc-GNPs exhibited a biphasic dose-response curve where concentrations up to 100 μg mL showed minimal cytotoxicity, whereas higher doses (>100 μg mL) were markedly cytotoxic. Cellular uptake was enhanced under serum-free conditions. Clonogenic survival assays revealed significant radiosensitization (sensitizer enhancement ratio up to 1.82 at 500 μg per mL Curc-GNPs), linked to an elevated -parameter in the linear-quadratic model and heightened reactive oxygen species production. These results highlight Curc-GNPs as a promising platform for enhancing radiotherapy efficacy in prostate cancer while potentially mitigating off-target toxicity.
前列腺癌仍然是男性癌症相关死亡的主要原因，三种主要治疗方式为手术、化疗、放疗，或根据分期联合使用。然而，放疗的应用常常受到危及器官的剂量限制毒性的制约。为应对这一挑战，我们开发了姜黄素包覆的金纳米颗粒（Curc-GNPs），其利用了金的光电特性和姜黄素的放射增敏作用。在本研究中，我们探究了Curc-GNP在PC-3前列腺癌细胞中的稳定性、细胞毒性、细胞摄取及放射增敏潜力。Curc-GNPs呈现出双相剂量反应曲线，浓度高达100 μg/mL时细胞毒性最小，而更高剂量（>100 μg/mL）则具有明显的细胞毒性。在无血清条件下细胞摄取增强。克隆形成存活试验显示出显著的放射增敏作用（在每毫升500 μg Curc-GNPs时增敏剂增强比高达1.82），这与线性二次模型中升高的参数及活性氧生成增加有关。这些结果突出了Curc-GNPs作为一个有前景的平台，可增强前列腺癌放疗疗效，同时可能减轻脱靶毒性。
