Extensive evaluations of the cytotoxic effects of gold nanoparticles

• Published in: Biochimica et biophysica acta Vol. 1830; no. 10; pp. 4960 - 4973
• Main Authors: Chuang, Show-Mei, Lee, Yi-Hui, Liang, Ruei-Yue, Roam, Gwo-Dong, Zeng, Zih-Ming, Tu, Hsin-Fang, Wang, Shi-Kwun, Chueh, Pin Ju
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2013
• Subjects: apoptosis; Apoptosis - drug effects; Base Sequence; cell communication; cell cycle; cell growth; Cell Line, Tumor; Cell-impedance measurement; Cytotoxicity; DNA microarray; DNA Primers; dose response; Drug Screening Assays, Antitumor; gene expression; gold; Gold - chemistry; Gold nanoparticle; Humans; impedance; In vitro assay; in vitro studies; mammals; Metal Nanoparticles - toxicity; monitoring; nanogold; nanoparticles; Oligonucleotide Array Sequence Analysis; proteins; reactive oxygen species; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; screening; toxicology; DNA microarray; In vitro assay; Cytotoxicity; Cell-impedance measurement; Gold nanoparticle
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2013.06.025

Many in vitro studies have revealed that the interference of dye molecules in traditional nanoparticle cytotoxicity assays results in controversial conclusions. The aim of this study is to establish an extensive and systematic method for evaluating biological effects of gold nanoparticles in mammalian cell lines. We establish the cell-impedance measurement system, a label-free, real-time cell monitoring platform that measures electrical impedance, displaying results as cell index values, in a variety of mammalian cell lines. Cytotoxic effects of gold nanoparticles are also evaluated with traditional in vitro assays. Among the six cell lines, gold nanoparticles induce a dose-dependent suppression of cell growth with different levels of severity and the suppressive effect of gold nanoparticles was indirectly associated with their sizes and cellular uptake. Mechanistic studies revealed that the action of gold nanoparticles is mediated by apoptosis induction or cell cycle delay, depending on cell type and cellular context. Although redox signaling is often linked to the toxicity of nanoparticles, in this study, we found that gold nanoparticle-mediated reactive oxygen species generation was not sustained to notably modulate proteins involved in antioxidative defense system. The cell-impedance measurement system, a dye-free, real-time screening platform, provides a reliable analysis for monitoring gold nanoparticle cytotoxicity in a variety of mammalian cell lines. Furthermore, gold nanoparticles induce cellular signaling and several sets of gene expression to modulate cellular physical processes. The systematic approach, such as cell-impedance measurement, analyzing the toxicology of nanomaterials offers convincing evidence of the cytotoxicity of gold nanomaterials. [Display omitted] •Cell-impedance measurement provides analyses to monitor dynamic effect of nanoparticles in a dye-free setting.•Traditional in vitro assays also support the cytotoxicity of gold nanoparticles.•Gold nanoparticles induce a dose-dependent suppression of cell growth with different levels of severity.•Gold nanoparticles specifically induce apoptosis or cell cycle delay depending on cell type.•Gold nanoparticles induce signaling and gene expression to modulate cellular responses.