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氧化石墨烯颗粒在体外实验中的生物安全性与血液相容性

Biosafety and Blood Compatibility of Graphene Oxide Particles in In Vitro Experiments.

作者信息

Prylutskyy Yuriy, Bełdzińska Patrycja, Derewońko Natalia, Halenova Tetiana, Raksha Nataliia, Zakrzewski Marcin, Gołuński Grzegorz, Prylutska Svitlana, Ritter Uwe, Savchuk Olexii, Piosik Jacek

机构信息

ESC "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, 01601 Kyiv, Ukraine.

Laboratory of Biophysics, University of Gdańsk, 80-307 Gdańsk, Poland.

出版信息

Materials (Basel). 2025 May 6;18(9):2128. doi: 10.3390/ma18092128.

DOI:10.3390/ma18092128
PMID:40363631
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12072977/
Abstract

Graphene oxide (GO), owing to its extraordinary application prospects in biomedicine, is attracting growing research attention. However, the biosafety and blood compatibility of GO required for its clearance for use in clinical trials remain elusive. Therefore, we studied the mutagenic properties of GO as well as its cell toxicity and blood compatibility. Prior to biological experiments, we assessed the structural organization of GO using dynamic light scattering and microscopic visualization methods. The results of both the Ames mutagenicity test performed on serovar Typhimurium TA98 and TA102 strains and the cytotoxicity test on noncancerous, immortalized human keratinocytes revealed no mutagenic or toxic effects of GO. Simultaneously, GO reduced the viability of the MelJuSo human melanoma cell line. A blood compatibility assay revealed that a concentration of 10 μg/mL was critical for GO biosafety, as greater concentrations induced diverse side effects. Specifically, GO disrupts erythrocytes' membranes in the dose-dependent manner. Moreover, GO at higher concentrations both inhibited the process of ADP (a physiological platelet agonist)-induced cell aggregation and affected their disaggregation process in platelet-rich plasma. However, in the blood clotting assessment, GO showed no effects on the activated partial thromboplastin time, prothrombin time, or thrombin time of the platelet-poor plasma. The obtained results clearly indicate that the relationship between the GO preparation method, its size, and concentration and biosafety must be cautiously monitored in the context of further possible biomedical applications.

摘要

氧化石墨烯(GO)因其在生物医学领域的非凡应用前景而受到越来越多的研究关注。然而,其用于临床试验所需的生物安全性和血液相容性仍不明确。因此,我们研究了GO的诱变特性及其细胞毒性和血液相容性。在进行生物学实验之前,我们使用动态光散射和显微镜可视化方法评估了GO的结构组织。对鼠伤寒沙门氏菌TA98和TA102菌株进行的Ames诱变试验以及对非癌性永生化人角质形成细胞的细胞毒性试验结果均显示GO无诱变或毒性作用。同时,GO降低了MelJuSo人黑色素瘤细胞系的活力。血液相容性分析表明,10μg/mL的浓度对GO的生物安全性至关重要,因为更高的浓度会引发多种副作用。具体而言,GO以剂量依赖的方式破坏红细胞膜。此外,较高浓度的GO既抑制了ADP(一种生理性血小板激动剂)诱导的细胞聚集过程,也影响了富含血小板血浆中血小板的解聚过程。然而,在凝血评估中,GO对乏血小板血浆的活化部分凝血活酶时间、凝血酶原时间或凝血酶时间均无影响。所得结果清楚地表明,在进一步可能的生物医学应用背景下,必须谨慎监测GO的制备方法、尺寸、浓度与生物安全性之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/8d71a7d38fbd/materials-18-02128-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/137ff0ceef37/materials-18-02128-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/4c76f7f95f54/materials-18-02128-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/f8a94d9fdbaa/materials-18-02128-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/0c3471748e18/materials-18-02128-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/45e1c1377a27/materials-18-02128-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/8d71a7d38fbd/materials-18-02128-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/137ff0ceef37/materials-18-02128-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/4c76f7f95f54/materials-18-02128-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/f8a94d9fdbaa/materials-18-02128-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/0c3471748e18/materials-18-02128-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/45e1c1377a27/materials-18-02128-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b05e/12072977/8d71a7d38fbd/materials-18-02128-g006.jpg

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本文引用的文献

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Nanomaterials (Basel). 2023 Sep 28;13(19):2666. doi: 10.3390/nano13192666.
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Multifunctional graphene oxide nanoparticles for drug delivery in cancer.多功能氧化石墨烯纳米粒子在癌症药物传递中的应用。
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An Insight into Recent Advances on Platelet Function in Health and Disease.
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Int J Mol Sci. 2022 May 27;23(11):6022. doi: 10.3390/ijms23116022.
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