Gutiérrez-Carcedo Patricia, Navalón Sergio, Simó Rafael, Setoain Xavier, Aparicio-Gómez Carolina, Abasolo Ibane, Victor Victor Manuel, García Hermenegildo, Herance José Raúl
Medical Molecular Imaging Research Group, Vall d'Hebron Research Institute, CIBBIM- Nanomedicine, Universitat Autònoma de Barcelona (UAB) and Biomedical Imaging Group, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), 08035 Barcelona, Spain.
Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Department of Endocrinology, Vall d'Hebron Research Institute, UAB, Biomedical Research Center in Diabetes Network and Associated Metabolic Diseases (CIBERDEM), 08035 Barcelona, Spain.
Nanomaterials (Basel). 2020 Apr 13;10(4):744. doi: 10.3390/nano10040744.
Ceria nanoparticles are cell compatible antioxidants whose activity can be enhanced by gold deposition and by surface functionalization with positive triphenylphosphonium units to selectively target the mitochondria. The antioxidant properties of these nanoparticles can serve as the basis of a new strategy for the treatment of several disorders exhibiting oxidative stress, such as cancer, diabetes or Alzheimer's disease. However, all of these pathologies require a specific antioxidant according with their mechanism to remove oxidant species excess in cells and diminish their effect on mitochondrial function. The mechanism through which ceria nanoparticles neutralize oxidative stress and their effect on mitochondrial function have not been characterized yet. In the present study, the mitochondria antioxidant effect of ceria and ceria-supported gold nanoparticles, with or without triphenylphosphonium functionalization, was assessed in HeLa cells. The effect caused by ceria nanoparticles on mitochondria function in terms of mitochondrial membrane potential (∆Ψm), adenosine triphosphate (ATP) production, nuclear respiratory factor 1 (NRF1) and nuclear factor erythroid-2-like 1 (NFE2L1) was reversed by the presence of gold. Furthermore, this effect was enhanced when nanoparticles were functionalized with triphenylphosphonium. Our study illustrates how the mitochondrial antioxidant effect induced by ceria nanoparticles can be modulated by the presence of gold.
二氧化铈纳米颗粒是具有细胞相容性的抗氧化剂，其活性可通过金沉积以及用正三苯基膦单元进行表面功能化来增强，从而选择性地靶向线粒体。这些纳米颗粒的抗氧化特性可作为一种新策略的基础，用于治疗多种表现出氧化应激的疾病，如癌症、糖尿病或阿尔茨海默病。然而，所有这些病症都需要根据其清除细胞内过量氧化物种并减轻其对线粒体功能影响的机制来使用特定的抗氧化剂。二氧化铈纳米颗粒中和氧化应激的机制及其对线粒体功能的影响尚未得到表征。在本研究中，评估了有或没有三苯基膦功能化的二氧化铈和二氧化铈负载金纳米颗粒对HeLa细胞的线粒体抗氧化作用。金的存在逆转了二氧化铈纳米颗粒对线粒体膜电位（∆Ψm）、三磷酸腺苷（ATP）产生、核呼吸因子1（NRF1）和核因子红细胞2样1（NFE2L1）方面线粒体功能的影响。此外，当纳米颗粒用三苯基膦功能化时，这种影响会增强。我们的研究说明了二氧化铈纳米颗粒诱导的线粒体抗氧化作用如何通过金的存在进行调节。
