Work

Enhancing radiation-resistance and peroxidase-like activity of single-atom copper nanozyme via local coordination manipulation

Year: 2024

Type: article

Abstract: The inactivation of natural enzymes by radiation poses a great challenge to their applications for radiotherapy. Single-atom nanozymes (SAzymes) with high structural stability under such extreme conditions become a promising candidate for replacing natural enzymes to shrink tumors. Here, we report a CuN 3 -centered SAzyme (CuN 3 -SAzyme) that exhibits higher peroxidase-like catalytic activity than a CuN 4 -centered counterpart, by locally regulating the coordination environment of single copper sites. Density functional theory calculations reveal that the CuN 3 active moiety confers optimal H 2 O 2 adsorption and dissociation properties, thus contributing to high enzymatic activity of CuN 3 -SAzyme. The introduction of X-ray can improve the kinetics of the decomposition of H 2 O 2 by CuN 3 -SAzyme. Moreover, CuN 3 -SAzyme is very stable after a total radiation dose of 500 Gy, without significant changes in its geometrical structure or coordination environment, and simultaneously still retains comparable peroxidase-like activity relative to natural enzymes. Finally, this developed CuN 3 -SAzyme with remarkable radioresistance can be used as an external field-improved therapeutics for enhancing radio-enzymatic therapy in vitro and in vivo. Overall, this study provides a paradigm for developing SAzymes with improved enzymatic activity through local coordination manipulation and high radioresistance over natural enzymes, for example, as sensitizers for cancer therapy.

Source: Nature Communications

DOI: 10.1038/s41467-024-50416-8