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银纳米颗粒在模型细胞系统中诱导的细胞损伤研究。

Investigation of Cell Damage Induced by Silver Nanoparticles in a Model Cell System.

作者信息

Pirutin Sergey, Chaikovskii Dmitrii, Shank Mikhail, Chivarzin Mikhail, Jia Shunchao, Yusipovich Alexander, Suvorov Oleg, Zhao Yuehong, Bezryadnov Dmitry, Rubin Andrey

机构信息

Faculty of Biology, Shenzhen MSU-BIT University, Shenzhen 518172, China.

Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, Russia.

出版信息

Pharmaceutics. 2025 Mar 21;17(4):398. doi: 10.3390/pharmaceutics17040398.

Abstract

: The growing diversity of novel nanoparticle synthesis methods, particularly for silver nanoparticles (AgNP), coupled with their significant biological activity and wide range of applications across various medical fields, necessitates a comprehensive investigation into the consequences of particle-induced cellular damage. This study aimed to investigate AgNP-induced damage to macrophage plasma membranes, focusing on concentration, temperature, incubation time, and the role of pro- and antioxidant factors, using model systems based on mouse peritoneal macrophages. Mouse peritoneal macrophages were incubated with AgNP (0.1-10 μg/mL) at temperatures ranging from 4 °C to 37 °C. Membrane integrity was assessed via microfluorimetric analysis. The influence of prooxidant (UV-B) and antioxidant (serotonin) factors was also examined. A mathematical model was developed to describe the interaction between AgNP and macrophages. The diameter of our synthesized silver nanoparticles, assessed via dynamic light scattering (DLS), ranged from 5 to 170 nm, with a predominant size distribution peak at 70 nm. AgNP caused dose- and temperature-dependent membrane damage, which was more pronounced at 4 °C and 37 °C than at 22 °C and increased with incubation time. UV-B enhanced membrane damage, while serotonin mitigated it. The mathematical model correlated strongly with the experimental data, emphasizing the role of ROS in membrane disruption. AgNP also dose-dependently increased ROS generation by macrophages. AgNP, in doses of 0.1-10 μg/mL, induces dose-dependent membrane damage in macrophages. The developed model is a useful tool for predicting nanoparticle toxicity. Together with the experimental findings, it highlights the critical role of ROS, lipid peroxidation, the lipid bilayer state, and antioxidant defenses in AgNP-induced membrane damage.

摘要

新型纳米颗粒合成方法的多样性不断增加,尤其是银纳米颗粒(AgNP)的合成方法,再加上其显著的生物活性以及在各个医学领域的广泛应用,有必要对颗粒诱导的细胞损伤后果进行全面研究。本研究旨在利用基于小鼠腹腔巨噬细胞的模型系统,研究AgNP对巨噬细胞质膜的损伤,重点关注浓度、温度、孵育时间以及促氧化和抗氧化因子的作用。将小鼠腹腔巨噬细胞与浓度为0.1 - 10μg/mL的AgNP在4℃至37℃的温度范围内孵育。通过微量荧光分析评估膜完整性。还研究了促氧化因子(UV - B)和抗氧化因子(血清素)的影响。开发了一个数学模型来描述AgNP与巨噬细胞之间的相互作用。通过动态光散射(DLS)评估,我们合成的银纳米颗粒直径范围为5至170nm,主要尺寸分布峰值在70nm。AgNP导致剂量和温度依赖性的膜损伤,在4℃和37℃时比在22℃时更明显,并且随孵育时间增加。UV - B增强了膜损伤,而血清素减轻了膜损伤。该数学模型与实验数据高度相关,强调了活性氧(ROS)在膜破坏中的作用。AgNP还剂量依赖性地增加巨噬细胞产生的ROS。剂量为0.1 - 10μg/mL的AgNP在巨噬细胞中诱导剂量依赖性的膜损伤。所开发的模型是预测纳米颗粒毒性的有用工具。连同实验结果一起,它突出了ROS、脂质过氧化、脂质双分子层状态和抗氧化防御在AgNP诱导的膜损伤中的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f305/12030423/77bb43bbbbd8/pharmaceutics-17-00398-g001.jpg

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