DNA-based FeCuAg nanoclusters with peroxidase-like and GSH depletion activities for toxicity of in vitro cancer cells

Abstract

Developing the efficient nanozymes for reactive oxygen species (ROS)-mediated highly potent tumor catalytic therapy has become a great challenge. In this study, we prepared the DNA-Fe, -FeAg, and -FeCuAg nanocluster (NCs) using the G-/C-rich single-stranded DNA (ssDNA) templates. The steady-state kinetic and the catalytic performances and mechanisms of DNA-metal NCs were first systematically investigated. The results indicated that c-kit-TBA-Fe, c-kit-TBA-FeAg, and c-kit-TBA-FeCuAg NCs exhibited the high peroxidase-like activity. All of three types of NCs presented the higher affinity to the substrate TMB and better storage stability at 4 °C than horseradish peroxidase (HRP). Moreover, c-kit-TBA-FeAg and c-kit-TBA-FeCuAg NCs presented the 6.7- and 4.7-fold stronger affinity to TMB than c-kit-TBA-Fe, respectively. However, the maximum reaction rate (V_max) of c-kit-TBA-FeCuAg NCs with H₂O₂ was the largest, which promoted the generation of much more ^•OH in the reaction system. More importantly, c-kit-TBA-FeCuAg NCs were able to deplete largely the intracellular GSH and thus generate lots of endogenous ROS in HeLa cells, thereby exhibiting the significant and specific in vitro cancer cells toxicity. Therefore, c-kit-TBA-FeCuAg NCs, with peroxidase-like activity and glutathione (GSH) consumption ability, hold the ROS-based promising therapeutic effects for cancer.

Keywords: Cancer treatment; DNA-based metal nanoclusters; GSH depletion; Nanozyme; ROS.