Enhancing Catalytic Activity of a Nickel Single Atom Enzyme by Polynary Heteroatom Doping for Ferroptosis-Based Tumor Therapy

Abstract

As a rising generation of nanozymes, single atom enzymes show significant promise for cancer therapy, due to their maximum atom utilization efficiency and well-defined electronic structures. However, it remains a tremendous challenge to precisely produce a heteroatom-doped single atom enzyme with an expected coordination environment. Herein, we develop an anion exchange strategy for precisely controlled production of an edge-rich sulfur (S)-and nitrogen (N)-decorated nickel single atom enzyme (S-N/Ni PSAE). In particular, sulfurized S-N/Ni PSAE exhibits stronger peroxidase-like and glutathione oxidase-like activities than the nitrogen-monodoped nickel single atom enzyme, which is attributed to the vacancies and defective sites of sulfurized nitrogen atoms. Moreover, both in vitro and in vivo results demonstrate that, compared with nitrogenmonodoped N/Ni PSAE, sulfurized S-N/Ni PSAE more effectively triggers ferroptosis of tumor cells via inactivating glutathione peroxidase 4 and inducing lipid peroxidation. This study highlights the enhanced catalytic efficacy of a polynary heteroatom-doped single atom enzyme for ferroptosis-based cancer therapy.

Engineering Single‐Atom Nanozymes for Catalytic Biomedical Applications

“…[70] Thus, Wu and co-workers improved the monodispersity and stability of the 900°C calcined nickel single atom enzyme (S-N/Ni SAzyme) via the hydrophobic interactions between the nanomaterials and DSPE-mPEG. [86] In addition to PEG, polyvinylpyrrolidone (PVP) is another commonly used ligand for surface functionalization. In comparison to PEG, PVP has a lower molecular weight and is more hydrophilic.…”

The applications of nanozymes in cancer therapy: based on regulating pyroptosis, ferroptosis and autophagy of tumor cells

“…Therefore, the polynary heteroatom-doped single-atom nanozyme S–N/Ni PSAE can effectively treat cancer by enhancing ferroptosis in tumor cells. 61 Zhu et al developed an FeN 4 -centered single-atom nanozyme (FeN 4 -SAzyme) and used it for radio-enzyme therapy with enhanced external-field catalysis. The FeN 4 -SAzyme nanozyme exhibited GPx-like activity, catalyzing the conversion of H 2 O 2 to ˙OH and Fe 2+ to Fe 3+ at the respective stoichiometric ratios, thereby depleting GSH in tumor cells.…”

Single-atom nanozymes as promising catalysts for biosensing and biomedical applications

“…11a). 167 As the tumor microenvironment features insufficient oxygen supply and excessive ROS (such as H 2 O 2 ), 168 one can take advantage of the unique activity of SAzymes to catalyze the decomposition of H 2 O 2 to cytotoxic hydroxyl radicals ( • OH) and locally kill the tumor cells. This was indeed demonstrated recently by He et al with a Pd SAzyme based on phenolic carbon quantum dot (DA-CQD@Pd).…”