关键词: Au−Fe3O4 nanoheterodimers MCF-10A MCF-7 Pd−Fe3O4 nanoheterodimers Pt−Fe3O4 nanoheterodimers caffeic acid multicellular tumor spheroids radiotherapy

Mesh : Breast / pathology Breast Neoplasms / drug therapy Female Humans Iron MCF-7 Cells Radiation-Sensitizing Agents / pharmacology Reactive Oxygen Species

来  源:   DOI:10.1021/acsabm.1c00803

Abstract:
The X-radiation enhancing effect of caffeic acid-functionalized Au-Fe3O4, Pt-Fe3O4, and Pd-Fe3O4 nanoheterodimers (NHDs) on 2D and 3D breast tumor (MCF-7) and healthy breast epithelial (MCF-10A) cells was comprehensively examined by performing cell viability, reactive oxygen species (ROS) detection, enzyme activity, and clonogenic assays. Intracellular NHDs were observed to cause DNA fragmentation and to enhance superoxide and hydroxyl radical formation in MCF-7 cells when exposed to a single dose of 1 Gy. MCF-7-derived multicellular tumor spheroids (MCF-7 MCTS) and MCF-10A-derived multicellular spheroids (MCF-10A MCS) were incubated with the NHDs and irradiated with five daily doses of 2 Gy. The Au-Fe3O4 and Pt-Fe3O4 NHD-loaded MCF-7 MCTS significantly decreased in volume after being exposed to fractionated irradiation, whereas intracellular Au-Fe3O4 and Pt-Fe3O4 NHDs promoted the growth of the irradiated MCF-10A MCS. Moreover, Au-Fe3O4 and Pt-Fe3O4 NHDs were shown to impede ROS formation and inhibit DNA strand breakage in the noncancerous MCF-10A cells. On the other hand, the Pd-Fe3O4 NHDs boosted X-radiation-induced damage of MCF-10 A cells, which was ascribed to impairment of the ROS scavenging enzyme activities. In summary, caffeic acid-functionalized Au-Fe3O4 and Pt-Fe3O4 NHDs performed as excellent X-radiation enhancing agents in breast tumor cells, while they protect healthy breast epithelial cells against X-radiation.
摘要:
咖啡酸功能化的Au-Fe3O4,Pt-Fe3O4和Pd-Fe3O4纳米异二聚体(NHDs)对2D和3D乳腺肿瘤(MCF-7)和健康乳腺上皮细胞(MCF-10A)的X射线增强作用通过执行细胞活力,活性氧(ROS)检测,酶活性,和克隆检测。当暴露于1Gy的单剂量时,观察到细胞内NHD会导致DNA断裂并增强MCF-7细胞中的超氧化物和羟基自由基形成。将MCF-7衍生的多细胞肿瘤球体(MCF-7MCTS)和MCF-10A衍生的多细胞球体(MCF-10AMCS)与NHD一起孵育,并用5个每日剂量的2Gy照射。Au-Fe3O4和Pt-Fe3O4NHD负载的MCF-7MCTS暴露于分馏辐照后,体积显着减少,而细胞内Au-Fe3O4和Pt-Fe3O4NHDs促进了辐照的MCF-10AMCS的生长。此外,在非癌性MCF-10A细胞中,Au-Fe3O4和Pt-Fe3O4NHD可阻止ROS形成并抑制DNA链断裂。另一方面,Pd-Fe3O4NHD增强了X辐射诱导的MCF-10A细胞损伤,这归因于ROS清除酶活性的损害。总之,咖啡酸官能化的Au-Fe3O4和Pt-Fe3O4NHD在乳腺肿瘤细胞中作为优异的X射线增强剂,同时保护健康的乳腺上皮细胞免受X射线辐射.
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