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不同粒径和表面涂层的磁性氧化铁纳米颗粒的遗传毒性评估。

Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings.

机构信息

National Chengdu Center for Safety Evaluation of Drugs, State Key Lab of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, People's Republic of China.

出版信息

Nanotechnology. 2014 Oct 24;25(42):425101. doi: 10.1088/0957-4484/25/42/425101. Epub 2014 Oct 2.

Abstract

Magnetic iron oxide nanoparticles (IONPs) have been widely used for various biomedical applications such as magnetic resonance imaging and drug delivery. However, their potential toxic effects, including genotoxicity, need to be thoroughly understood. In the present study, the genotoxicity of IONPs with different particle sizes (10, 30 nm) and surface coatings (PEG, PEI) were assessed using three standard genotoxicity assays, the Salmonella typhimurium reverse mutation assay (Ames test), the in vitro mammalian chromosome aberration test, and the in vivo micronucleus assay. In the Ames test, SMG-10 (PEG coating, 10 nm) showed a positive mutagenic response in all the five test bacterial strains with and without metabolic activation, whereas SEI-10 (PEI coating, 10 nm) showed no mutagenesis in all tester strains regardless of metabolic activation. SMG-30 (PEG coating, 30 nm) was not mutagenic in the absence of metabolic activation, and became mutagenic in the presence of metabolic activation. In the chromosomal aberration test, no increase in the incidence of chromosomal aberrations was observed for all three IONPs. In the in vivo micronucleus test, there was no evidence of increased micronuclei frequencies for all three IONPs, indicating that they were not clastogenic in vivo. Taken together, our results demonstrated that IONPs with PEG coating exhibited mutagenic activity without chromosomal and clastogenic abnormalities, and smaller IONPs (SMG-10) had stronger mutagenic potential than larger ones (SMG-30); whereas, IONPs with SEI coating (SEI-10) were not genotoxic in all three standard genotoxicity assays. This suggests that the mutagenicity of IONPs depends on their particle size and surface coating.

摘要

磁性氧化铁纳米粒子(IONPs)已广泛用于各种生物医学应用,如磁共振成像和药物输送。然而,它们的潜在毒性效应,包括遗传毒性,需要彻底了解。在本研究中,使用三种标准遗传毒性检测方法,即鼠伤寒沙门氏菌回复突变检测(Ames 试验)、体外哺乳动物染色体畸变检测和体内微核检测,评估了不同粒径(10、30nm)和表面涂层(PEG、PEI)的 IONPs 的遗传毒性。在 Ames 试验中,SMG-10(PEG 涂层,10nm)在有或没有代谢激活的情况下,在所有五个测试菌株中均表现出阳性致突变反应,而 SEI-10(PEI 涂层,10nm)在所有测试菌株中均无致突变性,无论是否有代谢激活。SMG-30(PEG 涂层,30nm)在没有代谢激活的情况下没有致突变性,而在有代谢激活的情况下则具有致突变性。在染色体畸变试验中,所有三种 IONPs 均未观察到染色体畸变发生率的增加。在体内微核试验中,所有三种 IONPs 均未显示微核频率增加,表明它们在体内没有致断裂作用。总之,我们的结果表明,具有 PEG 涂层的 IONPs 表现出致突变活性,而没有染色体和断裂异常,较小的 IONPs(SMG-10)比较大的 IONPs(SMG-30)具有更强的致突变潜力;而具有 SEI 涂层的 IONPs(SEI-10)在所有三种标准遗传毒性检测中均无遗传毒性。这表明 IONPs 的致突变性取决于其粒径和表面涂层。

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