CEREGE, UMR 7330, CNRS-Aix Marseille University, BP 80, 13545 Aix en Provence, France.
Chem Res Toxicol. 2012 Nov 19;25(11):2513-22. doi: 10.1021/tx3003214. Epub 2012 Oct 15.
Physical-chemical parameters such as purity, structure, chemistry, length, and aspect ratio of nanoparticles (NPs) are linked to their toxicity. Here, synthetic imogolite-like nanotubes with a set chemical composition but various sizes and shapes were used as models to investigate the influence of these physical parameters on the cyto- and genotoxicity and cellular uptake of NPs. The NPs were characterized using X-ray diffraction (XRD), small angle X-ray scattering (SAXS), and atomic force microscopy (AFM). Imogolite precursors (PR, ca. 5 nm curved platelets), as well as short tubes (ST, ca. 6 nm) and long tubes (LT, ca. 50 nm), remained stable in the cell culture medium. Internalization into human fibroblasts was observed only for the small particles PR and ST. None of the tested particles induced a significant cytotoxicity up to a concentration of 10(-1) mg·mL(-1). However, small sized NPs (PR and ST) were found to be genotoxic at very low concentration 10(-6) mg·mL(-1), while LT particles exhibited a weak genotoxicity. Our results indicate that small size NPs (PR, ST) were able to induce primary lesions of DNA at very low concentrations and that this DNA damage was exclusively induced by oxidative stress. The higher aspect ratio LT particles exhibited a weaker genotoxicity, where oxidative stress is a minor factor, and the likely involvement of other mechanisms. Moreover, a relationship among cell uptake, particle aspect ratio, and DNA damage of NPs was observed.
物理化学参数，如纳米粒子（NPs）的纯度、结构、化学性质、长度和纵横比，与它们的毒性有关。在这里，我们使用具有特定化学组成但具有不同大小和形状的合成似辉沸石纳米管作为模型，研究这些物理参数对 NPs 的细胞毒性、遗传毒性和细胞摄取的影响。使用 X 射线衍射（XRD）、小角 X 射线散射（SAXS）和原子力显微镜（AFM）对 NPs 进行了表征。Imogolite 前体（PR，约 5nm 弯曲的薄片）以及短管（ST，约 6nm）和长管（LT，约 50nm）在细胞培养基中保持稳定。只有小颗粒 PR 和 ST 被观察到能进入人成纤维细胞内。在 10（-1）mg·mL（-1）的浓度下，没有一种测试颗粒表现出明显的细胞毒性。然而，小尺寸 NPs（PR 和 ST）在非常低的浓度 10（-6）mg·mL（-1）下被发现具有遗传毒性，而 LT 颗粒表现出较弱的遗传毒性。我们的结果表明，小尺寸 NPs（PR、ST）能够在非常低的浓度下诱导 DNA 的初级损伤，这种 DNA 损伤仅由氧化应激引起。高纵横比的 LT 颗粒表现出较弱的遗传毒性，其中氧化应激是一个次要因素，可能涉及其他机制。此外，还观察到细胞摄取、颗粒纵横比和 NPs 的 DNA 损伤之间的关系。
