Cationic gold nanoparticles elicit mitochondrial dysfunction: a multi-omics study

• Published in: Scientific reports Vol. 9; no. 1; p. 4366
• Main Authors: Gallud, Audrey, Klöditz, Katharina, Ytterberg, Jimmy, Östberg, Nataliya, Katayama, Shintaro, Skoog, Tiina, Gogvadze, Vladimir, Chen, Yu-Zen, Xue, Ding, Moya, Sergio, Ruiz, Jaime, Astruc, Didier, Zubarev, Roman, Kere, Juha, Fadeel, Bengt
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.03.2019; Nature Publishing Group
• Subjects: 13/106; 14/19; 38/91; 631/80/82/23; 639/925/928/1065; 64/11; 82/58; 96/2; 96/31; Ammonium; Ammonium Compounds - chemistry; Apoptosis; Autophagy; Autophagy - drug effects; Cations - chemistry; Cations - pharmacology; Cell death; Cell Death - drug effects; Cell Line, Tumor; Chemical Phenomena; Cytotoxicity; Dose-Response Relationship, Drug; Gene Expression Profiling; Gold - chemistry; Gold - pharmacology; Humanities and Social Sciences; Humans; Lethality; Macrophages; Mass spectrometry; Mass spectroscopy; Medicin och hälsovetenskap; Metabolic Networks and Pathways; Metal Nanoparticles - chemistry; Metal Nanoparticles - ultrastructure; Mitochondria; Mitochondria - drug effects; Mitochondria - genetics; Mitochondria - metabolism; Mitochondria - ultrastructure; Monocytes; multidisciplinary; Nanoparticles; Oxidative Phosphorylation; Phagocytosis; Polyethylene glycol; Proteome; Proteomics; Proteomics - methods; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Sodium; Transcriptome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-40579-6

Systems biology is increasingly being applied in nanosafety research for observing and predicting the biological perturbations inflicted by exposure to nanoparticles (NPs). In the present study, we used a combined transcriptomics and proteomics approach to assess the responses of human monocytic cells to Au-NPs of two different sizes with three different surface functional groups, i . e ., alkyl ammonium bromide, alkyl sodium carboxylate, or poly(ethylene glycol) (PEG)-terminated Au-NPs. Cytotoxicity screening using THP-1 cells revealed a pronounced cytotoxicity for the ammonium-terminated Au-NPs, while no cell death was seen after exposure to the carboxylated or PEG-modified Au-NPs. Moreover, Au-NR3+ NPs, but not the Au-COOH NPs, were found to trigger dose-dependent lethality in vivo in the model organism, Caenorhabditis elegans . RNA sequencing combined with mass spectrometry-based proteomics predicted that the ammonium-modified Au-NPs elicited mitochondrial dysfunction. The latter results were validated by using an array of assays to monitor mitochondrial function. Au-NR3+ NPs were localized in mitochondria of THP-1 cells. Moreover, the cationic Au-NPs triggered autophagy in macrophage-like RFP-GFP-LC3 reporter cells, and cell death was aggravated upon inhibition of autophagy. Taken together, these studies have disclosed mitochondria-dependent effects of cationic Au-NPs resulting in the rapid demise of the cells.