Crucial role of chelatable iron in silver nanoparticles induced DNA damage and cytotoxicity

• Main Authors: Agnieszka Grzelak, Maria Wojewódzka, Sylwia Meczynska-Wielgosz, Mariusz Zuberek, Dominika Wojciechowska, Marcin Kruszewski
• Format: Article
• Language: English
• Published: Elsevier 2018-05-01
• Series: Redox Biology
• Subjects: Nanoparticle toxicity; ROS generation; Mitochondria; Iron; Fenton reaction
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213231717309138

Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O2•-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H2O2 instead of O2•-, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity. Altogether these results suggest that O2•- generated during NPs induced mitochondrial collapse is rapidly dismutated to H2O2, which in the presence of iron ions undergoes a Fenton reaction to produce an extremely reactive hydroxyl radical (•OH). Clarification of the mechanism of NPs-dependent generation of •OH and demonstration of the crucial role of iron ions in NPs toxicity will facilitate our understanding of NPs toxicity and the design of safe nanomaterials.