Gold nanorods (AuNRs) have shown their great potential in cancer treatment due to their special physiochemical and optical properties, and the ease of surface modification. However, the molecular mechanism of biological effects induced by different surface modified AuNRs
remains largely undetermined. Herein, we for the first time systematically analyzed metabolic impacts of three surface modified AuNRs in cancer and non-cancer cells detected by NMR and GC-FID/MS metabolomics and validated by molecular biological approach. We found that positively and negatively charged AuNRs induced different metabolic consequences.
Most importantly, we found that the PEI-AuNRs displayed specific cytotoxicity to A549 cells whilst posing little impact on 16HBE cells. The cytotoxicity of PEI-AuNRs to A549 cells is manifested in large disruptions to the cell metabolisms, which affects energy metabolism, choline metabolism, the hexosamine biosynthesis pathway and oxidative stress to cells. Our results provided comprehensive molecular information on the distinct biological effects of different surface modified AuNRs, and could be valuable in designing purpose-driven nanomaterials. Most importantly, this work highlighted the potential of metabolomics coupled
with molecular biological techniques in screening anti-tumor nanodrugs and revealing the molecular mechanism of their biological effects.