Stress-induced cytotoxicity of chiral Ag nanoclusters

We studied the cytotoxicity of Ag nanoclusters (Ag NCs) capped by the enantiomers l-glutathione (l-GSH) and d-glutathione (d-GSH) synthesized using the mild reduction agent tetrabutylammonium borohydride. The as-synthesized Ag NCs were characterized by HRTEM and UV-visible, photoluminescence and circular dichroism spectroscopy. The circular dichroism spectra of Ag NCs capped with l-GSH and d-GSH showed multiple bands that were identically mirror-imaged, demonstrating that both the metal core and the ligand contributed to the chirality of the GSH-capped NCs. The properties and potential applications of chiral Ag NCs in enantioselective catalysis and chiral recognition and sensing suggest that a comprehensive evaluation should be made of their potential toxicity. We found that Ag NCs capped with d-GSH (AgNCs@d-GSH) were more toxic to both human gastric cancer MGC-803 cells and human gastric mucous epithelial GES-1 cells than Ag NCs capped with l-GSH (AgNCs@l-GSH). Apoptosis also correlated well with the production of reactive oxygen species, mitochondrial membrane depolarization and G₂/M cell phase arrest in a dose- and chirality-dependent manner. The in vivo injection of AgNCs@l-GSH and AgNCs@d-GSH into mice bearing human gastric cancer xenografts led to a significant reduction in tumor size and increased apoptosis. This knowledge is important from the perspective of understanding the interactions between chiral nanoclusters and cells.