Fabrication and characterization of single-wall carbon nanotube and its biocompatibility to human hepatocytes

Hatef Rahim Sabbaghizadeh , Arshin Oskoueian , Amir Hossein Ashtari
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Abstract

Single-wall carbon nanotubes (SWCNTs) have emerged as promising nanocarriers for targeted cancer drug delivery due to their unique structural properties. However, their cytotoxicity remains a significant challenge, as the biocompatibility of SWCNTs with human cells, particularly hepatocytes, is crucial for their clinical application. The toxicity of SWCNTs is influenced by factors such as nanoparticle size, morphology, surface chemistry, and the presence of impurities. In this study, we aimed to synthesize highly pure SWCNTs and assess their biocompatibility with human hepatocyte cells.
SWCNTs were fabricated using a modified chemical vapor deposition (CVD) method, followed by a two-step acid purification technique. Raman spectroscopy and electron microscopy confirmed a high purity level of 99.8 %. The biocompatibility of the purified SWCNTs was evaluated using an in vitro model with human hepatocytes. Results indicated that high concentrations of SWCNTs (>50 μg/ml) significantly reduced cell viability, increased lactate dehydrogenase leakage, and elevated lipid peroxidation, while simultaneously suppressing antioxidant enzyme activity.
Flow cytometry analysis further revealed that exposure to high concentrations of SWCNTs induced apoptosis in hepatocytes. Molecular analysis of key biomarkers demonstrated upregulation of TNF-α, IL1β, NF-kB, and iNOS, alongside downregulation of nrf2 gene and protein expression. These alterations contribute to the mechanisms underlying SWCNT-induced oxidative stress and apoptosis in human hepatocyte cells. Despite the high purity of SWCNTs, their cytotoxic effects may be attributed to their inherent physical properties, including rigidity, surface area, and fiber length.
In conclusion, while SWCNTs hold great potential for cancer drug delivery, managing their toxicity remains critical for their future therapeutic applications.
单壁碳纳米管的制备、表征及其与人肝细胞的生物相容性
单壁碳纳米管(SWCNTs)由于其独特的结构特性而成为靶向癌症药物递送的有前途的纳米载体。然而,它们的细胞毒性仍然是一个重大挑战,因为SWCNTs与人类细胞(特别是肝细胞)的生物相容性对其临床应用至关重要。SWCNTs的毒性受纳米颗粒大小、形貌、表面化学和杂质存在等因素的影响。在本研究中,我们旨在合成高纯度的SWCNTs并评估其与人肝细胞的生物相容性。采用改进的化学气相沉积(CVD)方法制备SWCNTs,然后采用两步酸净化技术。拉曼光谱和电子显微镜证实纯度为99.8%。使用人肝细胞体外模型评估纯化SWCNTs的生物相容性。结果表明,高浓度SWCNTs (50 μg/ml)显著降低细胞活力,增加乳酸脱氢酶渗漏,升高脂质过氧化,同时抑制抗氧化酶活性。流式细胞术分析进一步显示,暴露于高浓度SWCNTs可诱导肝细胞凋亡。关键生物标志物的分子分析显示TNF-α、il - 1β、NF-kB和iNOS上调,同时nrf2基因和蛋白表达下调。这些改变有助于swcnts诱导人肝细胞氧化应激和凋亡的机制。尽管SWCNTs纯度高,但其细胞毒性作用可能归因于其固有的物理性质,包括刚性、表面积和纤维长度。总之,尽管SWCNTs在癌症药物递送方面具有巨大潜力,但管理其毒性对于其未来的治疗应用仍然至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
2.40
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