Slama Youssef, Arcambal Angelique, Septembre-Malaterre Axelle, Morel Anne-Laure, Pesnel Sabrina, Gasque Philippe
Université de La Réunion, Unité de Recherche Etudes Pharmaco-Immunologiques (EPI), CHU de La Réunion, Site Felix Guyon, Allée des Topazes, SC11021, 97400, Saint-Denis, La Réunion, France.
Clinique Sainte-Clotilde, Groupe Clinifutur, 127 Route de Bois de Nèfles, 97400, Saint-Denis, La Réunion, France.
Heliyon. 2024 Apr 5;10(8):e29297. doi: 10.1016/j.heliyon.2024.e29297. eCollection 2024 Apr 30.
In radiotherapy, metallic nanoparticles are of high interest in the fight against cancer for their radiosensitizing effects. This study aimed to evaluate the ability of core-shell FeO@Au nanoparticles to potentiate the irradiation effects on redox-, pro-inflammatory markers, and cell death of A549 human pulmonary cancer cells. The hybrid FeO@Au nanoparticles were synthesized using green chemistry principles by the sonochemistry method. Their characterization by transmission electron microscopy demonstrated an average size of 8 nm and a homogeneous distribution of gold. The decreased hydrodynamic size of these hybrid nanoparticles compared to magnetite (FeO) nanoparticles showed that gold coating significantly reduced the aggregation of FeO particles. The internalization and accumulation of the FeO@Au nanoparticles within the cells were demonstrated by Prussian Blue staining. The reactive oxygen species (ROS) levels measured by the fluorescent probe DCFH-DA were up-regulated, as well as mRNA expression of SOD, catalase, GPx antioxidant enzymes, redox-dependent transcription factor Nrf2, and ROS-producing enzymes (Nox2 and Nox4), quantified by RT-qPCR. Furthermore, irradiation coupled with FeO@Au nanoparticles increased the expression of canonical pro-inflammatory cytokines and chemokines (TNF-α, IL-1β, IL-6, CXCL8, and CCL5) assessed by RT-qPCR and ELISA. Hybrid nanoparticles did not potentiate the increased DNA damage detected by immunofluorescence following the irradiation. Nevertheless, FeO@Au caused cellular damage, leading to apoptosis through activation of caspase 3/7, secondary necrosis quantified by LDH release, and cell growth arrest evaluated by clonogenic-like assay. This study demonstrated the potential of FeO@Au nanoparticles to potentiate the radiosensitivity of cancerous cells.
在放射治疗中,金属纳米颗粒因其放射增敏作用而在抗癌斗争中备受关注。本研究旨在评估核壳型FeO@Au纳米颗粒增强对A549人肺癌细胞氧化还原、促炎标志物及细胞死亡的辐射效应的能力。采用声化学方法,依据绿色化学原理合成了杂化FeO@Au纳米颗粒。通过透射电子显微镜对其进行表征,结果显示平均粒径为8纳米,金分布均匀。与磁铁矿(FeO)纳米颗粒相比,这些杂化纳米颗粒的流体动力学尺寸减小,表明金涂层显著减少了FeO颗粒的聚集。通过普鲁士蓝染色证明了FeO@Au纳米颗粒在细胞内的内化和积累。用荧光探针DCFH-DA测定的活性氧(ROS)水平上调,通过RT-qPCR定量的超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶抗氧化酶、氧化还原依赖性转录因子Nrf2及产生活性氧的酶(Nox2和Nox4)的mRNA表达也上调。此外,RT-qPCR和ELISA评估显示,FeO@Au纳米颗粒与辐射联合作用增加了典型促炎细胞因子和趋化因子(TNF-α、IL-1β、IL-6、CXCL8和CCL5)的表达。杂化纳米颗粒并未增强辐射后免疫荧光检测到的DNA损伤增加。然而,FeO@Au导致细胞损伤,通过激活半胱天冬酶3/7导致细胞凋亡,通过乳酸脱氢酶释放定量的继发性坏死,以及通过克隆样试验评估的细胞生长停滞。本研究证明了FeO@Au纳米颗粒增强癌细胞放射敏感性的潜力。