Unexpected intracellular biodegradation and recrystallization of gold nanoparticles
Unexpected intracellular biodegradation and recrystallization of gold nanoparticles
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DOI：
10.1073/pnas.1911734116
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发表时间：
2020-01-07
影响因子：
11.1
通讯作者：
Carn, Florent
中科院分区：
文献类型：
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作者：
Balfourier, Alice;Luciani, Nathalie;Carn, Florent
金纳米粒子在生物医学应用中的应用范围越来越广。然而，人们对它们在生物体中的长期命运知之甚少，因为人们普遍承认，金纳米颗粒的惰性阻止了它们的生物降解。在这项工作中，监测了原代成纤维细胞捕获的金纳米颗粒在长达6个月的时间内的生物转化。结合电子显微镜成像和转录组学研究，揭示了一个意想不到的两步生物转化过程。首先是金纳米颗粒的降解，最小尺寸的金纳米颗粒消失得更快。这种降解是由NADPH氧化酶介导的，它在溶酶体中产生高度氧化的活性氧物种，并结合核因子红系2的细胞保护性表达。第二，金的重结晶过程产生生物矿化的纳米结构，由2.5 nm的晶体颗粒自组装成纳米叶。金属硫蛋白被强烈怀疑参与了阻止生物矿化的建筑，生物矿化在一个可能受螯合剂影响的过程中自组装。这些降解产物类似于50年前在金盐治疗后在活体中发现的金小体结构。总体而言，我们揭示了金纳米粒子生命周期中的几个步骤，在这些步骤中，细胞路径部分与离子金共享，揭示了常见的金代谢。
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.