Initiation of Protective Autophagy in Hepatocytes by Gold Nanorod Core /Silver Shell Nanostructures

The high reactivity of silver nanoparticles endows them with broad applications in the anti-bacterial fields, however, the safety of silver nanoparticles has attracted increasing public attention. After the exposure of silver nanoparticles in vivo, the liver can serve as a potential deposition site, however the potential biological effects of such nanoparticles on hepatocytes at low dosages are not well understood. Here, we study the interaction between gold nanorod core/silver shell nanostructures (Au@Ag NRs) and human hepatocytes, HepG2 cells, and determine that Au@Ag NRs at sub-lethal doses can induce autophagy. After uptake, Au@Ag NRs mainly localize to the lysosomes where they release silver ions and promote the production of reactive oxygen species (ROS). The ROS then depress AKT-mTOR signaling pathway and activate autophagy. In addition, the oxidative stress results in lysosomal impairment, causing decreased ability for lysosomal digestion. Moreover, the oxidative stress also affects the structure and function of mitochondria, leading to the initiation of protective autophagy to eliminate the damaged mitochondrion. Our study shows that at sub-lethal dosages, silver nanomaterials may alter physiological functions of hepatic cells by activating protective autophagy and cause potential health risks, indicating that cautious consideration of the safety of nanomaterials for certain application is necessary.