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

Abstract

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.

• Authors: Audrey Gallud, Katharina Klöditz, Jimmy Ytterberg, Nataliya Östberg, Shintaro Katayama, Tiina Skoog, Vladimir Gogvadze, Yu-Zen Chen, Ding Xue, Sergio Moya, Jaime Ruiz, Didier Astruc, Roman Zubarev, Juha Kere, Bengt Fadeel
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 4366 (03 13 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 30867451 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ammonium Compounds
• Cations
• Proteome
• Gold

Topics

• Ammonium Compounds (chemistry)
• Autophagy (drug effects)
• Cations (chemistry, pharmacology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Chemical Phenomena
• Dose-Response Relationship, Drug
• Gene Expression Profiling
• Gold (chemistry, pharmacology)
• Humans
• Metabolic Networks and Pathways
• Metal Nanoparticles (chemistry, ultrastructure)
• Mitochondria (drug effects, genetics, metabolism, ultrastructure)
• Oxidative Phosphorylation
• Proteome
• Proteomics (methods)
• Transcriptome