Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism

Silver nanoparticles (AgNPs) are widely applied in many household products and medical uses. However, studies on the effects of AgNPs on human health and environmental implications are in the beginning stage. Furthermore, most data on the toxicity of AgNPs have been generated using nanoparticles modified with detergents to prevent agglomeration, which may alter their toxicities. In this study, we studied toxicity using AgNPs prepared by dispersing them in fetal bovine serum (FBS), biocompatible materials. AgNPs (average size; 68.9 nm, concentrations; 0.2, 0.4, 0.8, and 1.6 ppm, exposure time; 24, 48, 72, and 96 h) showed cytotoxicity to cultured RAW264.7 cells by increasing sub G1 fraction, which indicates cellular apoptosis. AgNPs decreased intracellular glutathione level, increased NO secretion, increased TNF-α in protein and gene levels, and increased gene expression of matrix metalloproteinases (MMP-3, MMP-11, and MMP-19). When cells were treated with AgNPs, they were observed in the cytosol of the activated cells, but were not observed in the dead cells. It seemed that AgNPs were ionized in the cells to cause cytotoxicity by a Trojan-horse type mechanism suggested by previously reported studies.