Université de Strasbourg, CNRS, CAMB UMR 7199, F-67000 Strasbourg, France.
Université de Strasbourg, CNRS, Institut de Physique et Chimie des Matériaux Strasbourg, UMR 7504, F-67000 Strasbourg, France.
Int J Pharm. 2019 Feb 10;556:287-300. doi: 10.1016/j.ijpharm.2018.12.024. Epub 2018 Dec 14.
The engineering of iron oxide nanoparticles (IONPs) for biomedical use has received great interest over the past decade. In the present study we investigated the biocompatibility of IONPs grafted with linear (2P) or generation 1 (2PG1) or 2 (2PG2) dendronized oligoethyleneglycol units in THP-1-derived macrophages. To evaluate IONP effects on cell functionality and homeostasis, mitochondrial function (MTT assay), membrane permeability (LDH release), inflammation (IL-8), oxidative stress (reduced glutathione, GSH), NLRP3 inflammasome activation (IL-1β) and nanoparticle cellular uptake (intracellular iron content) were quantified after a 4-h or 24-h cell exposure to increasing IONP concentrations (0-300 µg Fe/mL). IONPs coated with a linear molecule, NP10COP@2P, were highly taken up by cells and induced significant dose-dependent IL-8 release, oxidative stress and NLRP3 inflammasome activation. In comparison, IONPs coated with dendrons of generation 1 (NP10COP@2PG1) and 2 (NP10COP@2PG2) exhibited better biocompatibility. Effect of the dendritic architecture of the surface coating was investigated in a kinetic experiment involving cell short-term exposure (30 min or 1 h 30) to the two dendronized IONPs. NP10COP@2PG2 disrupted cellular homeostasis (LDH release, IL-1β and IL-8 secretion) to a greater extend than NP10COP@2PG1, which makes this last IONP the best candidate as MRI contrast or theranostic agent.
在过去的十年中，人们对用于生物医学的氧化铁纳米粒子（IONP）的工程学产生了浓厚的兴趣。在本研究中，我们研究了接枝有线性（2P）或第一代（2PG1）或第二代（2PG2）树枝状低聚乙二醇单元的 IONP 在 THP-1 衍生的巨噬细胞中的生物相容性。为了评估 IONP 对细胞功能和动态平衡的影响，在细胞暴露于不同浓度 IONP（0-300μgFe/mL）4 小时或 24 小时后，通过 MTT 测定法、LDH 释放测定法、IL-8 测定法、氧化应激测定法（还原型谷胱甘肽，GSH）、NLRP3 炎症小体激活（IL-1β）和纳米颗粒细胞摄取（细胞内铁含量）来量化 IONP 对细胞的作用。用线性分子 NP10COP@2P 涂覆的 IONP 被细胞高度摄取，并诱导了明显的剂量依赖性 IL-8 释放、氧化应激和 NLRP3 炎症小体激活。相比之下，用第一代（NP10COP@2PG1）和第二代（NP10COP@2PG2）树枝状聚合物涂覆的 IONP 表现出更好的生物相容性。通过涉及细胞短期暴露（30 分钟或 1 小时 30 分钟）的动力学实验，研究了表面涂层的树枝状结构的影响。NP10COP@2PG2 比 NP10COP@2PG1 更能破坏细胞内的动态平衡（LDH 释放、IL-1β 和 IL-8 分泌），这使得最后一种 IONP 成为 MRI 造影剂或治疗剂的最佳候选物。
