Stelse-Masson Sarah, Lytvynenko Xenie, Bedregal-Portugal Kristel, Aubrun Clémentine, Lavaud Matéo, Kadri Malika, Jacquet Thibault, Moriscot Christine, Gallet Benoit, Chovelon Benoit, Coll Jean-Luc, Ravanat Jean-Luc, Mihóková Eva, Čuba Václav, Elleaume Hélène, Bulin Anne-Laure
Grenoble Alpes University, INSERM U1209, CNRS UMR5309, Institute for Advanced Biosciences, Cancer Targets and Experimental Therapeutics team, 38000 Grenoble, France.
Grenoble Alpes University, INSERM UA7, Synchrotron Radiation for Biomedicine, 38000 Grenoble, France.
Nanotheranostics. 2025 Jun 23;9(3):199-215. doi: 10.7150/ntno.115120. eCollection 2025.
Pancreatic cancer has a dismal prognosis and requires better treatments. One promising approach aims at improving radiotherapy using nanoscintillators, which down-convert ionizing radiation into visible light, triggering various radiotherapeutic effects upon X-ray irradiation. One such effect is radiation dose-enhancement, driven by high-Z elements present in the nanoscintillator core. These elements efficiently absorb X-rays, releasing secondary electrons that amplify the radiation dose in the surrounding tissue. In this paper, we study the ability of LuAlO:Pr@SiO, a lutetium-based nanoscintillator, to exert a radiation dose-enhancement effect in two human pancreatic cancer cell models, namely PANC-1 and MIA PaCa-2. LuAlO:Pr@SiO nanoparticles showed negligible toxicity up to 1 mg/mL in 2D and 3D models. Using monochromatic synchrotron radiation, we demonstrated that a subtoxic nanoparticle concentration enhances the radiation dose in 3D spheroids in an energy-dependent manner. These results were further supported by Monte Carlo simulations. Beyond this physical contribution, γ-H2AX foci quantification revealed a biological component to the radiosensitization: LuAlO:Pr@SiO nanoparticles not only amplified initial DNA damage, but also impaired its repair. These findings highlight the dual contribution of LuAlO:Pr@SiO nanoparticles to radiotherapy enhancement, combining both physical dose-enhancement and biological modulation of DNA repair.
胰腺癌的预后很差，需要更好的治疗方法。一种有前景的方法旨在利用纳米闪烁体改进放射治疗，纳米闪烁体可将电离辐射下转换为可见光，在X射线照射时引发各种放射治疗效果。其中一种效果是辐射剂量增强，由纳米闪烁体核心中存在的高Z元素驱动。这些元素有效吸收X射线，释放出二次电子，从而放大周围组织中的辐射剂量。在本文中，我们研究了基于镥的纳米闪烁体LuAlO:Pr@SiO在两种人类胰腺癌细胞模型（即PANC-1和MIA PaCa-2）中发挥辐射剂量增强效应的能力。在二维和三维模型中，LuAlO:Pr@SiO纳米颗粒在浓度高达1mg/mL时显示出可忽略不计的毒性。使用单色同步辐射，我们证明亚毒性纳米颗粒浓度以能量依赖的方式增强三维球体中的辐射剂量。蒙特卡罗模拟进一步支持了这些结果。除了这种物理作用外，γ-H2AX焦点定量揭示了放射增敏的生物学成分：LuAlO:Pr@SiO纳米颗粒不仅放大了初始DNA损伤，还损害了其修复。这些发现突出了LuAlO:Pr@SiO纳米颗粒对放射治疗增强的双重作用，将物理剂量增强和DNA修复的生物调节结合在一起。
