Citation: Jingyao Yu, Zhuoran Yang, Jian Jiang, Mengshu Xu, Chunyu Yang, Zhuo Li, Wei Guo. Engineering asymmetric electronic structures in Fe-N-S-C nanozymes for dual enzyme-catalyzed-induced ferroptosis and enhanced antitumor efficacy[J]. Chinese Chemical Letters, ;2026, 37(3): 111693. doi: 10.1016/j.cclet.2025.111693 shu

Engineering asymmetric electronic structures in Fe-N-S-C nanozymes for dual enzyme-catalyzed-induced ferroptosis and enhanced antitumor efficacy

Jingyao Yu ^{a, 1} ,
Zhuoran Yang ^{a, b, 1} ,
Jian Jiang ^c ,
Mengshu Xu ^a ,
Chunyu Yang ^{a, *,} ,
Zhuo Li ^{b, *,} ,
Wei Guo ^{a, *,}

a.
Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, China
b.
Key Laboratory of Functional Inorganic Materials Chemistry (Ministry of Education), School of Chemistry and Materials Science, International Joint Research Center for Catalytic Technology, Heilongjiang University, Harbin 150080, China
c.
Department of Ultrasound, Qunli Branch of The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China

ycy@hrbnu.edu.cn

lizhuo9410@hlju.edu.cn

guowei@hrbnu.edu.cn

Received Date: 24 May 2025
Revised Date: 6 August 2025
Accepted Date: 8 August 2025
Available Online: 9 August 2025

Figures(4)

Nanozymes, particularly single-atom nanozymes (SAzymes), have gained attention as potential ferroptosis inducers for cancer therapy due to their high catalytic efficiency and selectivity. However, the catalytic activity of SAzymes is often limited by the symmetrical electronic structure at their active sites. To enhance their performance, heteroatom doping strategies have been applied to modulate the electronic properties of SAzyme catalysts. In this study, we synthesized sulfur-doped FNS SAzymes with an Fe-N-S-C asymmetric coordination structure through pyrolysis. Enzyme kinetics analysis and density functional theory calculations revealed that FNS SAzymes exhibit highly efficient peroxidase-like and glutathione oxidase-like activities. These nanozymes are capable of catalyzing the decomposition of H₂O₂ to produce reactive oxygen species and depleting glutathione (GSH), thereby inducing ferroptosis. The FNS SAzymes were combined with an alkyl radical (^•R) initiator, 2,2-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH), and assembled into microneedle patches for enhanced ferroptosis therapy (FNSA-MN). Beyond the dual enzyme activities of FNS SAzymes, 808 nm laser activation induced a photothermal effect that facilitated the rapid dissociation of AIPH to generate ^•R. This FNSA-MN significantly enhanced lipid peroxidation within cells, thereby promoting ferroptosis. In vivo studies demonstrated significant suppression of tumor growth and strong anti-metastatic effects, highlighting a promising strategy for localized cancer therapy.
- Ferroptosis,
- Single-atom nanozymes,
- Lipid peroxidation,
- Density functional theory,
- Tumor therapy
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