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基于人原代单核细胞的新型体外模型评估工程纳米颗粒的免疫安全性。

Assessing the Immunosafety of Engineered Nanoparticles with a Novel in Vitro Model Based on Human Primary Monocytes.

机构信息

Institute of Protein Biochemistry, National Research Council , 80131 Napoli, Italy.

Institut Català de Nanotecnologia , Campus of the UAB, 08193 Bellaterra, Spain.

出版信息

ACS Appl Mater Interfaces. 2016 Oct 26;8(42):28437-28447. doi: 10.1021/acsami.6b06278. Epub 2016 Oct 13.

Abstract

The possibility that nanomaterials could perturb the normal course of an inflammatory response is a key issue when assessing nanoimmunosafety. The alteration of the normal progress of an inflammatory response may have pathological consequences, since inflammation is a major defensive mechanism and its efficiency maintains the body's health. The immunosafety of engineered nanoparticles at nontoxic concentrations was investigated with the use of a human primary monocyte-based in vitro system, which reproduces in a simplified fashion the full course of the physiological inflammatory response, from initiation and development to resolution. The kinetics of expression and production of inflammatory and anti-inflammatory cytokines and the proteomic profiles were used for describing the inflammatory defensive response. We assessed the ability of gold and silver nanoparticles to trigger inflammation and to interfere with the course of an ongoing defensive reaction. While neither nanoparticle type was able to directly activate monocytes, silver nanoparticles could exacerbate the inflammatory response of monocytes but did not interfere with the resolution of the inflammatory reaction. These findings support the use of human primary monocyte-based in vitro assays for realistically investigating the effects of engineered nanoparticles on human innate immune responses, in order to predict the immunological risk of nanomaterials and implement safe nanoparticle-based applications.

摘要

当评估纳米免疫安全性时,纳米材料是否可能干扰炎症反应的正常过程是一个关键问题。炎症反应的正常进程的改变可能具有病理后果,因为炎症是一种主要的防御机制,其效率维持着身体的健康。使用基于人原代单核细胞的体外系统研究了工程纳米颗粒在非毒性浓度下的免疫安全性,该系统以简化的方式再现了生理炎症反应的全过程,从启动、发展到解决。炎症和抗炎细胞因子的表达和产生动力学以及蛋白质组学图谱用于描述炎症防御反应。我们评估了金和银纳米颗粒引发炎症和干扰正在进行的防御反应过程的能力。虽然这两种纳米颗粒类型都不能直接激活单核细胞,但银纳米颗粒可以加重单核细胞的炎症反应,但不干扰炎症反应的解决。这些发现支持使用基于人原代单核细胞的体外测定法,真实地研究工程纳米颗粒对人类先天免疫反应的影响,以预测纳米材料的免疫风险并实施安全的基于纳米颗粒的应用。

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