orals 5th Asia-Pacific NMR Symposium 2013

Potential applications of metabonomics in nano-world (#80)

Yulan Wang 1
  1. Wuhan Institute of Physics and Mathematics, Wuhan, Hubei, China

Metabonomics is the science that studies dynamic alterations of metabolites in a cell, organ or entire organism1. The definition of the metabonomics was first given in 1999 as “the quantitative measurement of the time-related multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification”2. Technically, metabonomics investigations usually consist of the collection of metabolic profiles using nuclear magnetic resonance spectroscopy or mass spectrometry techniques and analysis of the collected data using appropriate multivariate statistical techniques. Recently, we have microscopically shown that protein-coated gold nanorods (Au NRs) was accumulated selectively in the mitochondria of cancer cells (A549) and caused tumor cell death, whereas posed negligible impact on normal cells (16HBE) (Wang et al. Nano Lett. 2011, 11, 772–780). Here, we demonstrate the metabonomic technique to screen nano-anticancer drugs. We found that protein-coated Au NR exposure caused a disruption in the intracellular environment of both A549 and 16HBE cells, which metabolically manifested in the reduction of lactate levels in both cell lines. In addition, protein-coated Au NRs induced oxidative stress in both cells lines. However, the 16HBE cells are more able to offset the oxidative stress than the A549 cells; this is because de novo GSH synthesis is triggered in protein-coated Au NR treated 16HBE cells but not in A549 cells, and the conversion of GSH to GSSG is more profound in 16HBE cells compared to A549 cells. The severe oxidative stress induces damage to mitochondria in A549 cells, leading to cell death, which is evident in the marked reduction in the levels of nucleosides and nucleotides. These findings provide molecular information for the distinctive responses of normal and tumor cells and highlighted the value of the metabonomics in assessment the biological effects of nano-drugs3.