posted on 2021-08-04, 12:03authored byLu Wang, Danielle F. Mello, Robert M. Zucker, Nelson A. Rivera, Nicholas M. K. Rogers, Nicholas K. Geitner, William K. Boyes, Mark R. Wiesner, Heileen Hsu-Kim, Joel N. Meyer
Silver nanoparticles (AgNPs) are
well-proven antimicrobial nanomaterials,
yet little is elucidated regarding the mechanism underlying cytotoxicity
induced by these nanoparticles. Here, we tested the hypothesis that
mitochondria are primary intracellular targets of two AgNPs and silver
ions in mouse hepatocytes (AML12) cultured in glucose- and galactose-based
media. AML12 cells were more sensitive to mitochondrial uncoupling
when grown with galactose rather than glucose. However, 24 h treatments
with 15 nm AgNPs and 6 nm GA-AgNPs (5 and 10 μg/mL) and AgNO3 (1 and 3 μg/mL), concentrations that resulted in either
10 or 30% cytotoxicity, failed to cause more toxicity to AML12 cells
grown on galactose than glucose. Furthermore, colocalization analysis
and subcellular Ag quantification did not show any enrichment of silver
content in mitochondria in either medium. Finally, the effects of
the same exposures on mitochondrial respiration were mild or undetectable,
a result inconsistent with mitochondrial toxicity causing cell death.
Our results suggest that neither ionic Ag nor the AgNPs that we tested
specifically target mitochondria and are inconsistent with mitochondrial
dysfunction being the primary cause of cell death after Ag exposure
under these conditions.