Pt-Coated Au Nanoparticle Toxicity Is Preferentially Triggered Via Mitochondrial Nitric Oxide/Reactive Oxygen Species in Human Liver Cancer (HepG2) Cells.

Abstract

Reactive nitrogen species (RNS) that are formed from the reaction of versatile nitric oxide (NO) with reactive oxygen species (ROS) have been less explored in potential cancer therapy. This may be partly due to the fewer available agents that could induce NO in cells. Here, we report platinum-coated gold nanoparticles (Pt-coated Au NPs; 27 ± 20 nm) as a strong inducer of NO (assessed by live-cell imaging under NO-specific DAR-1 probe labeling and indirectly using a Griess reagent) in human liver carcinoma (HepG2) cells. In addition to NO, this study found a critical role of ROS from mitochondrial sources in the mechanism of toxicity caused by Pt-coated Au NPs. Cotreatment with a thiol-replenishing general antioxidant NAC (N-acetyl cysteine) led to significant amelioration of oxidative stress against NP-induced toxicity. However, NAC did not exhibit as much ameliorative potential against NP-induced oxidative stress as the superoxide radical (O2•-)-scavenging mitochondrial specific antioxidant mito-TEMPO did. The higher protective potential of mito-TEMPO in comparison to NAC reveals mitochondrial ROS as an active mediator of NP-induced toxicity in HepG2 cells. Moreover, the relatively unaltered NP-induced NO concentration under cotreatment of GSH modulators NAC and buthionine sulfoximine (BSO) suggested that NO production due to NP treatment is rather independent of the cellular thiols at least in HepG2 cells. Moreover, toxicity potentiation by exogenous H2O2 again suggested a more direct involvement of ROS/RNS in comparison to the less potentiation of toxicity due to GSH-exhausting BSO. A steeper amelioration in NP-induced NO and ROS and, consequently, cytotoxicity by mito-TEMPO in comparison to NAC reveal a pronounced role of NO and ROS via the mitochondrial pathway in the toxicity of Pt-coated Au NPs in HepG2 cells.

• Authors: Mohd Javed Akhtar, Maqusood Ahamed, Hisham Alhadlaq, Salman Alrokayan
• Journal: ACS omega (ACS Omega) Vol. 6 Issue 23 Pg. 15431-15441 (Jun 15 2021) ISSN: 2470-1343 [Electronic] United States
• PMID: 34151121 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Published by American Chemical Society.