Gold nanourchins induce cellular stress, impair proteostasis and damage RNA

Abstract 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.