基于彗星法检测SPION诱导的人淋巴细胞DNA损伤

Swarupa Ghosh, Ilika Ghosh, A. Mukherjee
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摘要

超顺磁性氧化铁纳米粒子(SPION)被适当的生物相容性物质包裹,在各种生物医学领域,特别是在磁共振成像、组织工程、热疗和药物输送方面具有广泛的应用。在这项研究中,我们使用了两个新配制的SPIONs。利用二十二烷基二甲基溴化铵(DMAB)和±-生育酚乙二醇琥珀酸酯(TPGS)两种表面活性剂在SPIONs表面涂覆生物可降解聚合物聚乳酸共聚物(PLGA)进行表面修饰,拓展SPIONs在纳米医学领域的应用潜力。本研究的重点是评价两种配制的SPIONs中的任何一种对人淋巴细胞的遗传毒性。人淋巴细胞在37℃下,以每组11.2µg/ml浓度的铁暴露于SPIONs中3小时。采用MTT法对分离淋巴细胞进行单剂量毒性试验。未包被的SPIONs毒性很大,而包被的SPIONs细胞死亡明显减少。体外遗传毒性实验表明,制备的SPIONs在淋巴细胞中的尾DNA百分比明显低于未包被的SPIONs。结果表明,SPION诱导的遗传毒性完全取决于其物理化学性质。通过使用不同的涂层来调节这些特性可以降低毒性。表面修饰的类型主要决定了彗星试验检测到的DNA损伤的数量。结果还表明,SPION涂层具有生物相容性,适合在体内进行探索,而游离的SPION完全不适合在体内给药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comet assay based detection of SPION induced DNA damage in human lymphocytes
Superparamagnetic iron oxide nanoparticle (SPION) coated with suitable biocompatible substances have uses in various biomedical fields, particularly in magnetic resonance imaging, tissue engineering, hyperthermia and drug delivery. In this study we have used two newly formulated SPIONs. SPIONs were coated with biodegradable polymer polylactide co glycolide (PLGA) using of the two types of surfactants-didodecyldimethylammoniumbromide (DMAB) and ±-tocopheryl glycol succinate (TPGS) for surface modification, to extend the application potential in the field of nanomedicine. The present study focuses on the evaluation of genotoxicity if any of the two types of formulated SPIONs on human lymphocyte. Human lymphocytes were exposed to SPIONs at 11.2µg/ml concentrations of Fe in each group for 3 h at 37°C. Single-dose toxicity was tested in isolated lymphocytes using MTT assay. Uncoated SPIONs were found highly toxic while the coated ones showed significantly less cell death. In vitro genotoxicity of the formulated SPIONs showed significantly lower %tail DNA than uncoated SPIONs as detected by comet assay in lymphocytes. The results show that SPION induced genotoxicity is completely dependent on its physicochemical properties. Regulation of these properties by using different coatings could decrease toxicity. Type of surface modification primarily governed the amount of DNA damage as detected by Comet assay. The results also indicate that the coatings on the SPION were biocompatible and suitable for in vivo explorations while the free SPION were found completely unsuitable for in vivo administration.
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