Gold Nanoparticles of Diameter 1.4 nm Trigger Necrosis by Oxidative Stress and Mitochondrial Damage
Yu Pan
Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorAnnika Leifert
Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorDavid Ruau
Biomedical Engineering, Cell Biology RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorSabine Neuss
Pathology RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorJörg Bornemann
Electron Microscopy Facility, Medical Faculty RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorGünter Schmid
Inorganic Chemistry, University of Duisburg-Essen Universitätsstraβe 5–7, 45117 Essen (Germany)
Search for more papers by this authorWolfgang Brandau
Radiochemistry, University Hospital Essen Hufelandstraβe 55, 45122 Essen (Germany)
Search for more papers by this authorCorresponding Author
Ulrich Simon
Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Ulrich Simon, Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Willi Jahnen-Dechent, Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Search for more papers by this authorCorresponding Author
Willi Jahnen-Dechent
Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Ulrich Simon, Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Willi Jahnen-Dechent, Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Search for more papers by this authorYu Pan
Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorAnnika Leifert
Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorDavid Ruau
Biomedical Engineering, Cell Biology RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorSabine Neuss
Pathology RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorJörg Bornemann
Electron Microscopy Facility, Medical Faculty RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Search for more papers by this authorGünter Schmid
Inorganic Chemistry, University of Duisburg-Essen Universitätsstraβe 5–7, 45117 Essen (Germany)
Search for more papers by this authorWolfgang Brandau
Radiochemistry, University Hospital Essen Hufelandstraβe 55, 45122 Essen (Germany)
Search for more papers by this authorCorresponding Author
Ulrich Simon
Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Ulrich Simon, Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Willi Jahnen-Dechent, Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Search for more papers by this authorCorresponding Author
Willi Jahnen-Dechent
Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany)
Ulrich Simon, Inorganic Chemistry RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Willi Jahnen-Dechent, Biomedical Engineering, Biointerface Laboratory RWTH Aachen University Pauwelsstrasse 30, 52074 Aachen (Germany).
Search for more papers by this authorAbstract
Gold nanoparticles (AuNPs) are generally considered nontoxic, similar to bulk gold, which is inert and biocompatible. AuNPs of diameter 1.4 nm capped with triphenylphosphine monosulfonate (TPPMS), Au1.4MS, are much more cytotoxic than 15-nm nanoparticles (Au15MS) of similar chemical composition. Here, major cell-death pathways are studied and it is determined that the cytotoxicity is caused by oxidative stress. Indicators of oxidative stress, reactive oxygen species (ROS), mitochondrial potential and integrity, and mitochondrial substrate reduction are all compromised. Genome-wide expression profiling using DNA gene arrays indicates robust upregulation of stress-related genes after 6 and 12 h of incubation with a 2 × IC50 concentration of Au1.4MS but not with Au15MS nanoparticles. The caspase inhibitor Z-VAD-fmk does not rescue the cells, which suggests that necrosis, not apoptosis, is the predominant pathway at this concentration. Pretreatment of the nanoparticles with reducing agents/antioxidants N-acetylcysteine, glutathione, and TPPMS reduces the toxicity of Au1.4MS. AuNPs of similar size but capped with glutathione (Au1.1GSH) likewise do not induce oxidative stress. Besides the size dependency of AuNP toxicity, ligand chemistry is a critical parameter determining the degree of cytotoxicity. AuNP exposure most likely causes oxidative stress that is amplified by mitochondrial damage. Au1.4MS nanoparticle cytotoxicity is associated with oxidative stress, endogenous ROS production, and depletion of the intracellular antioxidant pool.
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