Insight on cytotoxic effects of silver nanoparticles: Alternative androgenic transactivation by adsorption with DHT

Silver nanoparticles (AgNPs) are accumulated in the male reproductive organs for a long time and cause several adverse effects in there. Up to now, there is little of information for the cytotoxic effects in male reproductive cells. In this study, the stable AgNPs with a minimal silver ion (Ag⁺) dissolution below concentration inducing cytotoxicity in the cell medium were exposed to the human prostate carcinoma cell line 22Rv1. Moreover particle uptake and androgen receptor (AR) transactivation were evaluated. In cell medium, AgNPs exhibited stability in an aqueous environment and minimal Ag⁺ release. Transmission electron microscopy (TEM) and energy dispersive spectrometer (EDS) analysis demonstrated uptake of AgNPs into cells via endocytosis, and a quantitative Ag assay showed that uptake of AgNPs was size-dependent with the majority of Ag retained in the particle form. To evaluate if the presence of AgNPs can change androgenic potentials of dihydrotestosterone (DHT, strong human androgen), we conducted an AR transactivation assay using the transgenic prostate cell line 22Rv1-MMTV-Hyg and found that AgNPs lowered androgenic transactivation of DHT, which is due to decreased bioavailability of DHT.