Federal State Budgetary Institution "Centre for Strategic Planning and Management of Biomedical Health Risks" of the Federal Medical Biological Agency, Pogodinskaya st. 10/1, Moscow 119435, Russia.
Federal State Budgetary Institution "Centre for Strategic Planning and Management of Biomedical Health Risks" of the Federal Medical Biological Agency, Pogodinskaya st. 10/1, Moscow 119435, Russia.
Biomed Pharmacother. 2024 Jun;175:116668. doi: 10.1016/j.biopha.2024.116668. Epub 2024 May 2.
The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence. Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model.
目前，放射治疗联合化学疗法是癌症患者治疗的标准方案。然而，安全剂量通常无法提供有效的治疗，因此，预先治疗的患者被迫重复治疗，而肿瘤对药物和辐射的耐药性通常已经增加。我们建议的解决方案之一是通过磁性氧化铁纳米颗粒（磁铁矿）增强肿瘤的放射敏感性来改善放射治疗的初始过程。我们获得了球形肝素化氧化铁纳米颗粒（hIONPs，约 20nm），并用 TEM、红外光谱和 DLS 对其进行了表征。然后，通过 XTT 测定法评估 hIONPs 对结肠癌细胞的细胞毒性，并通过 X 射线荧光分析纳米颗粒的细胞摄取。体外电离辐射（IR）与 hIONPs 的联合作用导致细胞周期 G2/M 期阻滞、有丝分裂错误增加和存活率降低（与单独暴露于 IR 和 hIONPs 的样品相比）。在 CT26 移植的 BALB/C 小鼠中，磁性导向 hIONPs 显示出有希望的结果：静脉注射 hIONPs 联合 IR 的组合的 T/C 比值为 20.8%（与未治疗的小鼠相比），而单独的放射治疗并没有显著降低肿瘤生长（72.4%）。无磁场导向的 hIONPs 与 IR 联合使用时，T/C 比值为 57.9%。这表明，超小尺寸和生物相容性分子并不是成功设计纳米药物的关键，在每种情况下，当转移到体内模型时，都需要改进输送技术。
