纳米颗粒介导的多柔比星药物递送在体外三维肿瘤球体中诱导分化集落失活。

Nanoparticle-Mediated Drug Delivery of Doxorubicin Induces a Differentiated Clonogenic Inactivation in 3D Tumor Spheroids In Vitro.

机构信息

Department of Life and Environmental Physics, National Institute for R&D in Physics and Nuclear Engineering "Horia Hulubei", Reactorului Street, 30, 077125 Magurele, Romania.

Department of Science and Engineering of Oxide Materials and Nanomaterials, Politehnica University of Bucharest, Gheorghe Polizu Street, 1-7, 011061 Bucharest, Romania.

出版信息

Int J Mol Sci. 2023 Jan 22;24(3):2198. doi: 10.3390/ijms24032198.

Involvement of 3D tumor cell models in the in vitro biological testing of novel nanotechnology-based strategies for cancer management can provide in-depth information on the real behavior of tumor cells in complex biomimetic architectures. Here, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the controlled delivery of a doxorubicin chemotherapeutic substance (IONP), and to enhance cytotoxicity of photon radiation therapy. The biological effects of nanoparticles and 150 kV X-rays were evaluated on both 2D and 3D cell models of normal human keratinocytes (HaCaT) and tumor cells-human cervical adenocarcinoma (HeLa) and human squamous carcinoma (FaDu)-through cell survival. In all 2D cell models, nanoparticles were similarly internalized in a peri-nuclear pattern, but resulted in different survival capabilities following radiation treatment. IONP on normal keratinocytes showed a protective effect, but a cytotoxic effect for cancer cells. In 3D tumor cell models, IONP were able to penetrate the cell spheroids towards the hypoxic areas. However, IONP and 150 kV X-rays led to a dose-modifying factor DMF = 1.09 ± 0.1 (200 µg/mL IONP) in HeLa spheroids, but to a radioprotective effect in FaDu spheroids. Results show that the proposed treatment is promising in the management of cervical adenocarcinoma.

在新型纳米技术癌症管理策略的体外生物学测试中，肿瘤细胞 3D 模型的参与可以为肿瘤细胞在复杂仿生结构中的真实行为提供深入信息。在这里，我们使用聚乙二醇包裹的氧化铁纳米颗粒来控制阿霉素化疗药物（IONP）的递送，并增强光辐射治疗的细胞毒性。通过细胞存活，评估了纳米颗粒和 150 kV X 射线对正常人类角质形成细胞（HaCaT）和肿瘤细胞-人宫颈腺癌（HeLa）和人鳞状细胞癌（FaDu）的 2D 和 3D 细胞模型的生物学效应。在所有 2D 细胞模型中，纳米颗粒都以核周模式被类似地内化，但在辐射处理后导致不同的存活能力。IONP 在正常角质形成细胞中表现出保护作用，但对癌细胞具有细胞毒性作用。在 3D 肿瘤细胞模型中，IONP 能够穿透细胞球体朝向缺氧区域。然而，IONP 和 150 kV X 射线导致 HeLa 球体中的剂量修正因子 DMF = 1.09 ± 0.1（200 µg/mL IONP），但在 FaDu 球体中具有放射保护作用。结果表明，所提出的治疗方法有望用于管理宫颈腺癌。