Department of Physiology, McGill University, Montreal, Canada.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Nanomedicine. 2019 Nov;22:102083. doi: 10.1016/j.nano.2019.102083. Epub 2019 Aug 9.
Gold nanoparticles have excellent potential for theranostic applications, but their impact on living cells is only partially understood. Many gold nanoparticles enter cells through endosomes/lysosomes which are linked to different cell organelles and compartments. Our study focuses on the unfolded protein response (UPR) in the endoplasmic reticulum (ER), cytoplasmic RNA-granules and proteostasis, because they are established indicators of cell stress and key regulators of cellular homeostasis. Using HeLa and renal proximal tubule cells as model systems, we show that gold nanourchins reduce cell proliferation, cause ER stress and impair proteostasis. Specifically, gold nanourchins activate the PERK-branch of the UPR, promote RNA oxidation, enhance P-body formation, and accumulate the oxidative stress marker Nrf2 and NFκB in nuclei. Taken together, our study demonstrates that gold nanourchins compromise ER, redox, protein, and RNA homeostasis. These insights provide new information on the cellular responses and molecular changes that gold nanourchins elicit in mammalian cells.
金纳米颗粒在治疗应用方面具有巨大的潜力，但它们对活细胞的影响还不完全清楚。许多金纳米颗粒通过内体/溶酶体进入细胞，内体/溶酶体与不同的细胞细胞器和隔室相连。我们的研究集中在内质网（ER）中的未折叠蛋白反应（UPR）、细胞质 RNA 颗粒和蛋白质稳态上，因为它们是细胞应激的既定指标，也是细胞内稳态的关键调节剂。使用 HeLa 和肾近端小管细胞作为模型系统，我们表明金纳米棒会降低细胞增殖，引起内质网应激并损害蛋白质稳态。具体来说，金纳米棒会激活 UPR 的 PERK 分支，促进 RNA 氧化，增强 P 体的形成，并使氧化应激标志物 Nrf2 和 NFκB 在核内积累。总之，我们的研究表明金纳米棒会破坏内质网、氧化还原、蛋白质和 RNA 的稳态。这些发现为金纳米棒在哺乳动物细胞中引起的细胞反应和分子变化提供了新的信息。
