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超顺磁性氧化铁纳米颗粒(SPIONs)通过靶向口腔鳞状细胞癌(OSCC)的线粒体对其产生选择性毒性。

The selective toxicity of superparamagnetic iron oxide nanoparticles (SPIONs) on oral squamous cell carcinoma (OSCC) by targeting their mitochondria.

作者信息

Afrasiabi Mona, Seydi Enayatollah, Rahimi Shabnam, Tahmasebi Ghazaleh, Jahanbani Jahanfar, Pourahmad Jalal

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Occupational Health and Safety Engineering, School of Health, Alborz University of Medical Sciences, Karaj, Iran.

出版信息

J Biochem Mol Toxicol. 2021 Jun;35(6):1-8. doi: 10.1002/jbt.22769. Epub 2021 Mar 11.

DOI:10.1002/jbt.22769
PMID:33704875
Abstract

In recent years, many researchers have made tremendous efforts into using nanotechnology in biomedical applications and science, such as magnetic resonance imaging, drug delivery, and in particular, oncological therapeutic via superparamagnetic iron oxide nanoparticles (SPIONs). Head and neck squamous cell carcinoma (HNSCC) and especially oral squamous cell carcinoma (OSCC) have been a serious and ongoing concern. There are many strong emphases on the importance of toxic mechanisms due to oxidative stress and specifically, the changed cellular response. Therefore, our study was designed to evaluate the effects of SPIONs on OSCC mitochondria because of the usefulness of the application of these nanoparticles in cancer treatment and diagnosis. An increased level of reactive oxygen species (ROS) is one of the substantial mechanisms found for SPIONs in this study, and initially originated from disruption of the electron transfer chain shown by a decrease in mitochondrial succinate dehydrogenase activity. Increased ROS formation subsequently followed a decline of mitochondrial membrane potential, the release of mitochondrial cytochrome complex, and mitochondrial swelling in the OSCC mitochondria compared with almost no effect in normal mitochondria. In addition, the SPIONs decreased cell viability and increased lipid peroxidation level and caspase-3 activity in OSCC cells. The results represented that the exposure to the SPIONs induced selective toxicity only on the OSCC but not normal mitochondria. Based on our findings, we finally concluded that the SPIONs may be considered as a potential therapeutic candidate for the treatment of OSCC.

摘要

近年来,许多研究人员在将纳米技术应用于生物医学应用和科学领域做出了巨大努力,如磁共振成像、药物递送,尤其是通过超顺磁性氧化铁纳米颗粒(SPIONs)进行肿瘤治疗。头颈部鳞状细胞癌(HNSCC),尤其是口腔鳞状细胞癌(OSCC)一直是一个严重且持续存在的问题。人们非常重视氧化应激导致的毒性机制的重要性,特别是细胞反应的变化。因此,由于这些纳米颗粒在癌症治疗和诊断中的应用价值,我们的研究旨在评估SPIONs对OSCC线粒体的影响。活性氧(ROS)水平升高是本研究中发现的SPIONs的重要作用机制之一,最初源于线粒体琥珀酸脱氢酶活性降低所显示的电子传递链的破坏。与正常线粒体几乎无影响相比,ROS生成增加随后伴随着OSCC线粒体膜电位下降、线粒体细胞色素复合物释放和线粒体肿胀。此外,SPIONs降低了OSCC细胞的活力,增加了脂质过氧化水平和caspase-3活性。结果表明,暴露于SPIONs仅对OSCC而非正常线粒体诱导了选择性毒性。基于我们的研究结果,我们最终得出结论,SPIONs可被视为治疗OSCC的潜在候选治疗药物。

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