Laboratoire de Conception et Application de Molécules Bioactives, Faculté de Pharmacie, UMR 7199, CNRS-Université de Strasbourg, Illkirch, France.
Laboratoire de Bioimagerie et Pathologies, Faculté de Pharmacie, UMR 7021, CNRS-Université de Strasbourg, Illkirch, France.
J Nanobiotechnology. 2021 Jan 6;19(1):5. doi: 10.1186/s12951-020-00747-7.
A positive surface charge has been largely associated with nanoparticle (NP) toxicity. However, by screening a carbon NP library in macrophages, we found that a cationic charge does not systematically translate into toxicity. To get deeper insight into this, we carried out a comprehensive study on 5 cationic carbon NPs (NP2 to NP6) exhibiting a similar zeta (ζ) potential value (from + 20.6 to + 26.9 mV) but displaying an increasing surface charge density (electrokinetic charge, Q from 0.23 to 4.39 µmol/g). An anionic and non-cytotoxic NP (NP1, ζ-potential = - 38.5 mV) was used as control.
The 5 cationic NPs induced high (NP6 and NP5, Q of 2.95 and 4.39 µmol/g, respectively), little (NP3 and NP4, Q of 0.78 and 1.35 µmol/g, respectively) or no (NP2, Q of 0.23 µmol/g) viability loss in THP-1-derived macrophages exposed for 24 h to escalating NP dose (3 to 200 µg/mL). A similar toxicity trend was observed in airway epithelial cells (A549 and Calu-3), with less viability loss than in THP-1 cells. NP3, NP5 and NP6 were taken up by THP-1 cells at 4 h, whereas NP1, NP2 and NP4 were not. Among the 6 NPs, only NP5 and NP6 with the highest surface charge density induced significant oxidative stress, IL-8 release, mitochondrial dysfunction and loss in lysosomal integrity in THP-1 cells. As well, in mice, NP5 and NP6 only induced airway inflammation. NP5 also increased allergen-induced immune response, airway inflammation and mucus production.
Thus, this study clearly reveals that the surface charge density of a cationic carbon NP rather than the absolute value of its ζ-potential is a relevant descriptor of its in vitro and in vivo toxicity.
正表面电荷在很大程度上与纳米颗粒（NP）毒性有关。然而，通过在巨噬细胞中筛选碳 NP 文库，我们发现阳离子电荷并不系统地转化为毒性。为了更深入地了解这一点，我们对 5 种带正电荷的碳 NP（NP2 到 NP6）进行了全面研究，它们具有相似的 ζ 电位值（+20.6 至+26.9 mV），但显示出越来越高的表面电荷密度（动电电荷，Q 从 0.23 到 4.39 μmol/g）。我们使用带负电荷且无细胞毒性的 NP（NP1，ζ 电位=-38.5 mV）作为对照。
在 24 小时内，暴露于递增 NP 剂量（3 至 200 μg/mL）下，5 种阳离子 NP（NP6 和 NP5 的 Q 值分别为 2.95 和 4.39 μmol/g）分别诱导 THP-1 衍生巨噬细胞发生高（NP6 和 NP5）、低（NP3 和 NP4）或无（NP2）活力损失。在气道上皮细胞（A549 和 Calu-3）中也观察到类似的毒性趋势，与 THP-1 细胞相比，活力损失较小。NP3、NP5 和 NP6 在 4 小时内被 THP-1 细胞摄取，而 NP1、NP2 和 NP4 则未被摄取。在这 6 种 NP 中，只有具有最高表面电荷密度的 NP5 和 NP6 诱导 THP-1 细胞产生显著的氧化应激、IL-8 释放、线粒体功能障碍和溶酶体完整性丧失。同样，在小鼠中，只有 NP5 和 NP6 诱导气道炎症。NP5 还增加了变应原诱导的免疫反应、气道炎症和粘液产生。
因此，本研究清楚地表明，阳离子碳 NP 的表面电荷密度而不是其 ζ 电位的绝对值是其体外和体内毒性的相关描述符。
