Laboratoire Matière et Systèmes Complexes, CNRS, Université de Paris, Paris 75205 Cedex 13, France.
Laboratoire Matériaux et Phénomènes Quantiques, CNRS, Université de Paris, Paris 75205 Cedex 13, France.
Proc Natl Acad Sci U S A. 2020 Jan 7;117(1):103-113. doi: 10.1073/pnas.1911734116. Epub 2019 Dec 18.
Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism.
金纳米颗粒在不断扩大的生物医学应用领域得到了应用。然而，由于普遍认为金纳米颗粒的惰性可防止其生物降解，因此人们对其在生物体中的长期归宿知之甚少。在这项工作中，研究人员在长达 6 个月的时间里监测了被原代成纤维细胞捕获的金纳米颗粒的生物转化。电子显微镜成像和转录组学研究的结合揭示了一个出人意料的两步生物转化过程。首先，金纳米颗粒发生降解，最小尺寸的颗粒消失得更快。这种降解是由 NADPH 氧化酶介导的，该酶在溶酶体中产生高度氧化的活性氧物质，同时核因子 erythroid 2 表达也具有细胞保护作用。其次，金的再结晶过程产生了生物矿化纳米结构，由 2.5nm 的结晶颗粒自组装成纳米叶。强烈怀疑金属硫蛋白参与了生物矿化的构建块，这些构建块自组装成一个可能受螯合剂影响的过程。这些降解产物与 50 年前金盐治疗后在体内发现的金硫蛋白结构相似。总的来说，我们揭示了金纳米颗粒生命周期中的步骤，其中细胞途径与离子金部分共享，揭示了一种共同的金代谢。
