Department of Life and Environmental Physics, "Horia Hulubei" National Insitute of Physics and Nuclear Engineering (IFIN-HH), 30 Reactorului Street, 077125 Magurele, Romania.
Department of Science and Engineering of Oxide Materials and Nanomaterials, "Politehnica" University of Bucharest (UPB), 1-7 Polizu Street, 011061 Bucharest, Romania.
Int J Mol Sci. 2020 Sep 30;21(19):7220. doi: 10.3390/ijms21197220.
This study aims to investigate whether ionizing radiation combined with doxorubicin-conjugated iron oxide nanoparticles (NP-DOX) improves the internalization and cytotoxic effects of the nano-carrier-mediated drug delivery in MG-63 human osteosarcoma cells. NP-DOX was designed and synthesized using the co-precipitation method. Highly stable and crystalline nanoparticles conjugated with DOX were internalized in MG-63 cells through macropinocytosis and located in the perinuclear area. Higher nanoparticles internalization in MG-63 cells previously exposed to 1 Gy X-rays was correlated with an early accumulation of cells in G/M, starting at 12 h after treatment. After 48 h, the application of the combined treatment led to higher cytotoxic effects compared to the individual treatment, with a reduction in the metabolic capacity and unrepaired DNA breaks, whilst a low percent of arrested cells, contributing to the commitment of mitotic catastrophe. NP-DOX showed hemocompatibility and no systemic cytotoxicity, nor histopathological alteration of the main organs.
本研究旨在探讨电离辐射联合阿霉素偶联氧化铁纳米颗粒（NP-DOX）是否能提高纳米载体介导的药物输送在 MG-63 人骨肉瘤细胞中的内化和细胞毒性作用。NP-DOX 通过共沉淀法设计和合成。高度稳定和结晶的 DOX 偶联纳米颗粒通过巨胞饮作用被内化到 MG-63 细胞中，并位于核周区。先前暴露于 1 Gy X 射线的 MG-63 细胞中更高的纳米颗粒内化与细胞在 G/M 期的早期积累相关，从处理后 12 小时开始。48 小时后，与单独治疗相比，联合治疗导致更高的细胞毒性作用，表现为代谢能力下降和未修复的 DNA 断裂，而阻滞细胞的比例较低，有助于有丝分裂灾难的发生。NP-DOX 显示出良好的血液相容性，没有全身细胞毒性，也没有主要器官的组织病理学改变。
