Gold nanorods are one of the most widely explored inorganic materials in nanomedicine for diagnostics, therapeutics and sensing¹. It has been shown that gold nanorods are not cytotoxic and localize within cytoplasmic vesicles following endocytosis, with no nuclear localization^2,3, but other studies have reported alterations in gene expression profiles in cells following exposure to gold nanorods, via unknown mechanisms⁴. In this work we describe a pathway that can contribute to this phenomenon. By mapping the intracellular chemical speciation process of gold nanorods, we show that the commonly used Au–thiol conjugation, which is important for maintaining the noble (inert) properties of gold nanostructures, is altered following endocytosis, resulting in the formation of Au(i)–thiolates that localize in the nucleus⁵. Furthermore, we show that nuclear localization of the gold species perturbs the dynamic microenvironment within the nucleus and triggers alteration of gene expression in human cells. We demonstrate this using quantitative visualization of ubiquitous DNA G-quadruplex structures, which are sensitive to ionic imbalances, as an indicator of the formation of structural alterations in genomic DNA.

金纳米棒是用于诊断，治疗和传感^1的纳米医学中使用最广泛的无机材料之一。有研究表明，金纳米棒对细胞内吞后无细胞毒性，并位于细胞质囊泡内，无核定位[ ^2,3]，但其他研究报道了金纳米棒暴露后细胞中基因表达谱的改变，其机制尚不清楚[ ^4]。。在这项工作中，我们描述了可能导致这种现象的途径。通过绘制金纳米棒的细胞内化学形态过程的图谱，我们表明，内吞作用后改变了常用的金-硫醇共轭，这对于保持金纳米结构的高贵（惰性）特性很重要，它会发生内吞作用而发生改变，从而导致Au（i）–定位于原子核⁵中的硫醇盐。此外，我们表明，金物种的核定位扰乱了细胞核内的动态微环境，并触发了人类细胞中基因表达的改变。我们使用对离子不平衡敏感的普遍存在的DNA G-四链体结构的定量可视化来证明这一点，作为对基因组DNA中结构改变形成的指示。