Enhancement of nanozyme activity by second ligand modification on glutathione protected gold nanoclusters for regulation of intracellular oxidative stress

Nanozymes, as an alternative to natural enzymes, have received wide interests in recent years. Here, we have separated two main glutathione protected gold nanoclusters (GSH-Au NCs), namely, high fluorescent species with low peroxidase-like activity, and low fluorescent species with high peroxidase-like activity, from NCs prepared using different ratios of precursors. Additionally, the peroxidase-like activity of the latter species can be regulated by surface modification of a second thiolate ligand. As a representative, L-cysteine (L-Cys) modified GSH-Au NCs may exhibit both enhanced peroxidase-like activity (up to 5-fold) and improved fluorescent properties (similar to 3.3-fold) compared with GSH-Au NCs. The cytotoxicity and reactive oxygen species (ROS) level detection demonstrate that L-Cys modified NCs may cause effective cytotoxicity on breast cancer cells through the selective ROS generation. This study further expands the peroxidase-like kinetics of surface modified Au NCs and provides a new possibility for regulating the level of oxidative stress in cells.