Issue

Vol. 18 (2026)

Innovative Strategies to Overcome Stability Challenges of Single-Atom Nanozymes

https://doi.org/10.1007/s40820-025-01939-2
Rong Guo
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, People’s Republic of China
Qiuzheng Du
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, People’s Republic of China
Yaping He
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, People’s Republic of China
Haoan Wu
State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering and Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, People’s Republic of China
Yu Zhang
State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering and Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, People’s Republic of China
Ziwei Jing
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, People’s Republic of China

Corresponding Author: Ziwei Jing

fccjingzw@zzu.edu.cn

Nano-Micro Letters, Vol. 18 (2026), Article Number: 100

Abstract

Single-atom nanozymes (SAzymes) exhibit exceptional catalytic efficiency due to their maximized atom utilization and precisely modulated metal-carrier interactions, which have attracted significant attention in the biomedical field. However, stability issues may impede the clinical translation of SAzymes. This review provides a comprehensive overview of the applications of SAzymes in various biomedical fields, including disease diagnosis (e.g., biosensors and diagnostic imaging), antitumor therapy (e.g., photothermal therapy, photodynamic therapy, sonodynamic therapy, and immunotherapy), antimicrobial therapy, and anti-oxidative stress therapy. More importantly, the existing challenges of SAzymes are discussed, such as metal atom clustering and active site loss, ligand bond breakage at high temperature, insufficient environment tolerance, biosecurity risks, and limited catalytic long-term stability. Finally, several innovative strategies to address these stability concerns are proposed—synthesis process optimization (space-limited strategy, coordination site design, bimetallic synergistic strategy, defect engineering strategy, atom stripping-capture), surface modification, and dynamic responsive design—that collectively pave the way for robust, clinically viable SAzymes.


Highlights:
1 This review uniquely provides an in-depth focus on the stability issues of single-atom nanozymes (SAzymes), covering multiple aspects such as metal atom clustering and active site loss, ligand bond breakage at high temperature, insufficient environment tolerance, biosecurity risks, and limited catalytic long-term stability.
2 This review integrates and systematically discusses a wide range of potential strategies to overcome stability issues, including synthesis process optimization (space-limited strategy, coordination site design, bimetallic synergistic strategy, defect engineering strategy, atom stripping-capture), surface modification, and dynamic responsive design.
3 To transform SAzymes from “star materials” of the laboratory into precise clinical tools for medicine, the authors propose the four-dimensional roadmap: structure-predictable, activity-tunable, biocompatible, and scalable.

Keywords

Single-atom nanozymes Clinical translation Stability issues Innovative strategies Biocompatibility
Guo, Rong, Qiuzheng Du, Yaping He, Haoan Wu, Yu Zhang, and Ziwei Jing. 2026. “Innovative Strategies to Overcome Stability Challenges of Single-Atom Nanozymes”. Nano-Micro Letters 18 (January):100. https://doi.org/10.1007/s40820-025-01939-2.
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