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氨基和羧基功能化介孔硅对血管内皮细胞的细胞毒性。

Cytotoxicity of mesoporous silica modified by amino and carboxyl groups on vascular endothelial cells.

机构信息

Department of Occupational and Environmental Health, School of Public Health and Management, Ningxia Medical University, Yinchuan, Ningxia, China.

出版信息

Environ Toxicol. 2021 Jul;36(7):1422-1433. doi: 10.1002/tox.23138. Epub 2021 Mar 25.

DOI:10.1002/tox.23138
PMID:33764655
Abstract

Mesoporous silica is widely used because of its unique and excellent properties, especially it can be used as a drug carrier and gene carrier in the biomedical field. After the mesoporous silica is put into clinical use, it is more likely to be exposed in human body. Therefore, the effect of mesoporous silica on human body cannot be ignored. The injury of vascular endothelial cells is a prerequisite for the occurrence of many cardiovascular diseases. As a drug and gene carrier, mesoporous silica increases its contact with vascular endothelial cells, so its toxic effect on cardiovascular system cannot be ignored. In this study, amino (NH ) and carboxyl (COOH) were modified on mesoporous silica SBA-15 by post-grafting. The results showed that it still maintained the one-dimensional hexagonal mesoporous structure of SBA-15 and had typical mesoporous structure. Then human umbilical vein endothelial cells (HUVECs) were infected with SBA-15, NH -SBA-15, and COOH-SBA-15. The results showed that the functionalized mesoporous silica SBA-15 had cytotoxicity to HUVECs and damaged the cell membrane, but compared with the unmodified mesoporous silica SBA-15 the cytotoxicity of functionalized mesoporous silica SBA-15 was lower and the toxicity of carboxyl modified group was the lowest. By comparing the cell inhibition rate and the expression level of lactate dehydrogenate and reactive oxygen species induced by the three materials, oxidative damage and cell membrane damage may be two mechanisms of cytotoxicity. Mesoporous silica SBA-15 has an effect on cardiovascular system by inducing the high expression of nitric oxide, intercellular adhesive molecule-1 and vascular cell adhesive molecule-1 in HUVECs. In summary, our results show that mesoporous silica is toxic to vascular endothelial cells.

摘要

介孔硅由于其独特而优异的性能而被广泛应用,特别是在生物医学领域可用作药物载体和基因载体。介孔硅投入临床使用后,在人体中更容易被暴露。因此,介孔硅对人体的影响不容忽视。血管内皮细胞的损伤是许多心血管疾病发生的前提。作为药物和基因载体,介孔硅增加了与血管内皮细胞的接触,因此其对心血管系统的毒性作用不容忽视。本研究通过后嫁接法在介孔硅 SBA-15 上修饰了氨基(-NH2)和羧基(-COOH)。结果表明,它仍然保持了 SBA-15 的一维六方介孔结构,具有典型的介孔结构。然后用 SBA-15、NH2-SBA-15 和 COOH-SBA-15 感染人脐静脉内皮细胞(HUVECs)。结果表明,功能化介孔硅 SBA-15 对 HUVECs 具有细胞毒性,破坏了细胞膜,但与未修饰的介孔硅 SBA-15 相比,功能化介孔硅 SBA-15 的细胞毒性较低,羧基修饰基团的毒性最低。通过比较三种材料诱导的细胞抑制率和乳酸脱氢酶和活性氧的表达水平,氧化损伤和细胞膜损伤可能是细胞毒性的两种机制。介孔硅 SBA-15 通过诱导 HUVECs 中一氧化氮、细胞间黏附分子-1 和血管细胞黏附分子-1 的高表达对心血管系统产生影响。综上所述,我们的结果表明介孔硅对血管内皮细胞有毒性。

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