Cytotoxic response of platinum-coated gold nanorods in human breast cancer cells at very low exposure levels

Environ Toxicol. 2016 Nov;31(11):1344-1356. doi: 10.1002/tox.22140. Epub 2015 Apr 6.

Abstract

Because of unique optical behavior gold nanorods (GNRs) have attracted attention for the application in biomedical field such as bio-sensing, bio-imaging and hyperthermia. However, toxicological response of GNRs is controversial due to their different surface coating. Therefore, a comprehensive knowledge about toxicological profile of GNRs is necessary before their biomedical applications. First time, we investigated the toxic response of GNRs coated with platinum (GNRs-Pt) in human breast carcinoma (MCF-7) cells. Platinum coating further improves the optical and catalytic properties of GNRs. Assays such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), neutral red uptake (NRU) and lactate dehydroganase (LDH) assays have shown that GNRs-Pt induced cytotoxicity at very low exposure levels (0.1-0.8 μg mL-1 ). Accumulation of cells in SubG1 phase and low mitochondrial membrane potential (JC-1 probe) in treated cells suggest that GNRs-Pt induced cell death via apoptotic pathway. Quantitative real-time PCR data demonstrated that mRNA expression of apoptotic genes (bax, caspase-3 and caspase-9) were up-regulated while anti-apoptotic gene bcl-2 was down-regulated in cells exposed to GNRs-Pt. We further observed the higher activity of caspase-3 and caspase-9 enzymes in GNRs-Pt treated cells supporting mRNA data. Moreover, N-acetyl cysteine (NAC) significantly attenuated the ROS generation and cytotoxicity induced by GNRs-Pt in MCF-7 cells suggesting that ROS might plays a crucial role in GNRs-Pt induced toxicity. This study warns of possible toxicity of GNRs even at very low exposure levels. Further investigations needed to explore potential mechanisms of this low dose toxicity phenomenon. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1344-1356, 2016.

Keywords: gold nanorods; human health; low exposure levels; platinum coating; toxicity.

MeSH terms

  • Acetylcysteine / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Down-Regulation / drug effects
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Gold / chemistry*
  • Humans
  • MCF-7 Cells
  • Membrane Potential, Mitochondrial / drug effects
  • Nanotubes / chemistry*
  • Nanotubes / toxicity
  • Particle Size
  • Platinum / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation / drug effects

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Reactive Oxygen Species
  • Platinum
  • Gold
  • Caspase 3
  • Caspase 9
  • Acetylcysteine