Revealing silver cytotoxicity using Au nanorods/Ag shell nanostructures: disrupting cell membrane and causing apoptosis through oxidative damage

Silver nanoparticles (NPs) have been widely explored as antibacterial and antifungal agents in households, cosmetics, food packaging, medical devices and even various wound care products. With the application of silver NPs in biomedicine expanding, the safety issue is attracting ever-growing attention. Although increasing literatures have evidenced that silver NPs induce reactive oxygen species (ROS) in mammalian cells and thus resulted in cell damage, mechanisms of how these nanoparticles initiate ROS accumulation are open questions. In this work, we found an important pathway of initiating ROS overproduction. Gold nanorod core/silver shell nanostructures (herein termed as Ag nanorods, AgNRs) were employed as a model for silver NPs and NIH3T3 fibroblast cell line was chosen as mammalian cell model. Upon exposure to the AgNRs, the cell membrane of the fibroblasts was disrupted along with generation of malondialdehyde (MDA), possibly due to the dissolution of silver ions from AgNRs surface. Consequently, actin depolymerization in the cytoskeleton connecting tightly with the membrane occurred. The membrane damage allowed calcium influx and induced intracellular calcium overload, which further caused ROS overproduction and mitochondrial membrane potential variation. All these complex stresses eventually resulted in cell death through apoptosis in a dose-dependent manner.