Future Industries Institute, University of South Australia, Mawson Lakes, South Australia, Australia.
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Nat Nanotechnol. 2021 Aug;16(8):926-932. doi: 10.1038/s41565-021-00914-3. Epub 2021 May 13.
Our knowledge of uptake, toxicity and detoxification mechanisms as related to nanoparticles' (NPs') characteristics remains incomplete. Here we combine the analytical power of three advanced techniques to study the cellular binding and uptake and the intracellular transformation of silver nanoparticles (AgNPs): single-particle inductively coupled mass spectrometry, mass cytometry and synchrotron X-ray absorption spectrometry. Our results show that although intracellular and extracellularly bound AgNPs undergo major transformation depending on their primary size and surface coating, intracellular Ag in 24 h AgNP-exposed human lymphocytes exists in nanoparticulate form. Biotransformation of AgNPs is dominated by sulfidation, which can be viewed as one of the cellular detoxification pathways for Ag. These results also show that the toxicity of AgNPs is primarily driven by internalized Ag. In fact, when toxicity thresholds are expressed as the intracellular mass of Ag per cell, differences in toxicity between NPs of different coatings and sizes are minimized. The analytical approach developed here has broad applicability in different systems where the aim is to understand and quantify cell-NP interactions and biotransformation.
我们对纳米颗粒（NPs）特性相关的摄取、毒性和解毒机制的了解仍然不完整。在这里，我们结合了三种先进技术的分析能力来研究银纳米颗粒（AgNPs）的细胞结合和摄取以及细胞内转化：单颗粒电感耦合质谱、质谱流式细胞术和同步辐射 X 射线吸收光谱法。我们的结果表明，尽管细胞内外结合的 AgNPs 会根据其原始尺寸和表面涂层发生重大转化，但在 24 小时 AgNP 暴露的人类淋巴细胞中，细胞内的 Ag 以纳米颗粒的形式存在。AgNPs 的生物转化主要由硫化作用主导，这可以被视为 Ag 的一种细胞解毒途径。这些结果还表明，AgNPs 的毒性主要是由内化的 Ag 驱动的。事实上，当毒性阈值以每个细胞内的 Ag 质量表示时，不同涂层和尺寸的 NPs 之间的毒性差异最小化。这里开发的分析方法在不同的系统中具有广泛的适用性，目的是理解和量化细胞-NP 相互作用和生物转化。
