Selective metabolic effects of gold nanorods on normal and cancer cells and their application in anticancer drug screening

Abstract

Cetyltrimethylammonim bromide coated gold nanorods (Au NRs) has a potential to become anti-cancer nano-drugs. Previously, the comparative responses of human alveolar adenocarcinoma epithelial cells (A549) and normal bronchial epithelial cells (16HBE) exposed to Au NRs have been characterized. It has been shown that Au NRs are translocated from the lysosome to the mitochondria in A549 cells but not in normal 16HBE cell lines. However, the molecular information during this cellular translocation remains largely undetermined. Here, we have used a metabonomic technique to comparatively analyze the time-dependent metabolic changes in Au NRs-induced A549 and 16HBE. We found that Au NRs 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, 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 Au NRs 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. Furthermore, significantly elevated levels of amino acids are likely due to stress hormones being produced in Au NRs treated cells. These findings provide comprehensive molecular information on the distinctive intracellular localization, cellular uptake and translocation of Au NRs in normal and tumor cells, highlighting the value of metabonomics in assessing biological effects of nano-drugs.