Efficient double-stranded hydrolysis of plasmid DNA by molybdenum sulfide quantum dots under mild conditions.

The development of inorganic DNA-cleavage reagents has been an area of active research. However, despite extensive efforts, an efficient method for degrading DNA, such as antibiotic resistance genes (ARGs), has not yet been developed because of its high hydrolytic stability. Herein, we present our results demonstrating that molybdenum sulfide quantum dots (MoS2 QDs) can effectively catalyze the cleavage and degradation of double-stranded DNA under mild conditions (pH 7.4, 37 °C) without requiring external energy. Notably, structure-activity analysis indicates that the nuclease-mimicking activity of the MoS2 QDs is attributed to the cooperative effects of their crystal structure (phase), sulfur vacancies (S-vacancies), and Lewis acidity. Superior DNA nuclease activity is achieved in the 1T-phase MoS2 QDs with a higher density of S-vacancies. Unexpectedly, biochemical assays reveal that MoS2 QDs cleave DNA through phosphate ester hydrolysis, rather than through reactive oxygen species-mediated oxidation, functioning as DNA hydrolases. Furthermore, we demonstrate that MoS2 QDs significantly suppress the horizontal transfer of ARGs. This study provides a strategy for designing nanozymes with nuclease activities, advancing their development as a new class of agents for eliminating environmental ARGs and preventing the emergence of resistant bacteria.