Silver nanoparticles induce cytotoxicity by releasing Ag + from the lysosome and increasing lysosomal membrane permeability

Abstract

Silver nanoparticles (AgNPs) have been widely used in many productions. Previous studies have shown partly AgNPs cytotoxicity in vitro and in vivo; however, the mechanism of this cytotoxicity has not been identified. Our study proved that AgNPs reached the lysosomes after contact with human fibroblasts. Cytotoxicity gradually increased as AgNPs enrichment in the lysosomes, accompanied by a reduction in lysosomal membrane permeability (LMP) and an increase in intracellular silver ion (Ag+). Inhibiting LMP or chelating Ag+ can effectively reduce AgNP toxicity. It has been confirmed that AgNPs gradually increased in the liver and spleen after subcutaneous injection, accompanied by the abnormal of liver function. Inhibition of LMP or chelation of Ag+in vivo can effectively protect liver and renal functions, and this protective effects showed a good synergistic effect. Our studies will provide theoretical support for more reasonable and safe clinical applications of AgNPs.