Refining Single-Atom Catalytic Kinetics for Tumor Homologous-Targeted Catalytic Therapy
Corresponding Author: Peng Huang
Nano-Micro Letters,
Vol. 17 (2025), Article Number: 253
Abstract
Single-atom nanozymes (SAzymes) hold significant potential for tumor catalytic therapy, but their effectiveness is often compromised by low catalytic efficiency within tumor microenvironment. This efficiency is mainly influenced by key factors including hydrogen peroxide (H2O2) availability, acidity, and temperature. Simultaneous optimization of these key factors presents a significant challenge for tumor catalytic therapy. In this study, we developed a comprehensive strategy to refine single-atom catalytic kinetics for enhancing tumor catalytic therapy through dual-enzyme-driven cascade reactions. Iridium (Ir) SAzymes with high catalytic activity and natural enzyme glucose oxidase (GOx) were utilized to construct the cascade reaction system. GOx was loaded by Ir SAzymes due to its large surface area. Then, the dual-enzyme-driven cascade reaction system was modified by cancer cell membranes for improving biocompatibility and achieving tumor homologous targeting ability. GOx catalysis reaction could produce abundant H2O2 and lower the local pH, thereby optimizing key reaction-limiting factors. Additionally, upon laser irradiation, Ir SAzymes could raise local temperature, further enhancing the catalytic efficiency of dual-enzyme system. This comprehensive optimization maximized the performance of Ir SAzymes, significantly improving the efficiency of catalytic therapy. Our findings present a strategy of refining single-atom catalytic kinetics for tumor homologous-targeted catalytic therapy.
Highlights:
1 Developed a dual-enzyme cascade system integrating iridium single-atom nanozymes with glucose oxidase, optimizing hydrogen peroxide production, acidity, and temperature within the tumor microenvironment to markedly improve catalytic therapy efficacy.
2 Functionalized the cascade reaction system with cancer cell membranes to achieve homologous targeting and high biocompatibility, ensuring accurate accumulation at tumor sites while minimizing off-target effects.
Keywords
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G. Feng, H. Huang, M. Zhang, Z. Wu, D. Sun et al., Single atom iron-doped graphic-phase C3N4 semiconductor nanosheets for augmented sonodynamic melanoma therapy synergy with endowed chemodynamic effect. Adv. Sci. 10(23), e2302579 (2023). https://doi.org/10.1002/advs.202302579
J. Zhou, D. Xu, G. Tian, Q. He, X. Zhang et al., Coordination-driven self-assembly strategy-activated Cu single-atom nanozymes for catalytic tumor-specific therapy. J. Am. Chem. Soc. 145(7), 4279–4293 (2023). https://doi.org/10.1021/jacs.2c13597
H. Yang, M. Luo, S. Lu, Q. Zhang, Y. Chao et al., Low-temperature aerobic oxidation of thiophenic sulfides over atomic Mo hosted by cobalt hydroxide sub-nanometer sheets. Chem 8(9), 2460–2471 (2022). https://doi.org/10.1016/j.chempr.2022.06.001
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J. Liu, A. Wang, S. Liu, R. Yang, L. Wang et al., A titanium nitride nanozyme for pH-responsive and irradiation-enhanced cascade-catalytic tumor therapy. Angew. Chem. Int. Ed. 60(48), 25328–25338 (2021). https://doi.org/10.1002/anie.202106750
L. Yang, S. Dong, S. Gai, D. Yang, H. Ding et al., Deep insight of design, mechanism, and cancer theranostic strategy of nanozymes. Nano-Micro Lett. 16(1), 28 (2023). https://doi.org/10.1007/s40820-023-01224-0
J. Cui, F. Zhang, D. Yan, T. Han, L. Wang et al., “Trojan horse” phototheranostics: fine-engineering NIR-II AIEgen camouflaged by cancer cell membrane for homologous-targeting multimodal imaging-guided phototherapy. Adv. Mater. 35(33), 2302639 (2023). https://doi.org/10.1002/adma.202302639
B. Geng, J. Hu, Y. Li, S. Feng, D. Pan et al., Near-infrared phosphorescent carbon dots for sonodynamic precision tumor therapy. Nat. Commun. 13(1), 5735 (2022). https://doi.org/10.1038/s41467-022-33474-8
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J. Wu, Y. Zhang, K. Jiang, X. Wang, N.T. Blum et al., Enzyme-engineered conjugated polymer nanoplatform for activatable companion diagnostics and multistage augmented synergistic therapy. Adv. Mater. 34(18), e2200062 (2022). https://doi.org/10.1002/adma.202200062
T. He, H. Xu, Y. Zhang, S. Yi, R. Cui et al., Glucose oxidase-instructed traceable self-oxygenation/hyperthermia dually enhanced cancer starvation therapy. Theranostics 10(4), 1544–1554 (2020). https://doi.org/10.7150/thno.40439
C. Yang, M.R. Younis, J. Zhang, J. Qu, J. Lin et al., Programmable NIR-II photothermal-enhanced starvation-primed chemodynamic therapy using glucose oxidase-functionalized ancient pigment nanosheets. Small 16(25), e2001518 (2020). https://doi.org/10.1002/smll.202001518
X. Zhang, X. Chen, Y. Zhao, Nanozymes: versatile platforms for cancer diagnosis and therapy. Nano-Micro Lett. 14(1), 95 (2022). https://doi.org/10.1007/s40820-022-00828-2
J. Kohout, Modified Arrhenius equation in materials science, chemistry and biology. Molecules 26(23), 7162 (2021). https://doi.org/10.3390/molecules26237162
M. Zandieh, J.W. Liu, Nanozymes: Definition, activity, and mechanisms. Adv. Mater. 36, 2211041 (2024). https://doi.org/10.1002/adma.202211041
R. Zhang, B. Xue, Y. Tao, H. Zhao, Z. Zhang et al., Edge-site engineering of defective Fe-N4 nanozymes with boosted catalase-like performance for retinal vasculopathies. Adv. Mater. 34(39), e2205324 (2022). https://doi.org/10.1002/adma.202205324
J. Cheng, L. Li, D. Jin, Y. Dai, Y. Zhu et al., Boosting ferroptosis therapy with iridium single-atom nanocatalyst in ultralow metal content. Adv. Mater. 35(17), e2210037 (2023). https://doi.org/10.1002/adma.202210037
Q. Hu, W. Zhu, J. Du, H. Ge, J. Zheng et al., A GPX4-targeted photosensitizer to reverse hypoxia-induced inhibition of ferroptosis for non-small cell lung cancer therapy. Chem. Sci. 14(34), 9095–9100 (2023). https://doi.org/10.1039/d3sc01597a
J. Liu, S. Dong, S. Gai, Y. Dong, B. Liu et al., Design and mechanism insight of monodispersed AuCuPt alloy nanozyme with antitumor activity. ACS Nano 17(20), 20402–20423 (2023). https://doi.org/10.1021/acsnano.3c06833
D. Deng, C. Xu, P. Sun, J. Wu, C. Yan et al., Crystal structure of the human glucose transporter GLUT1. Nature 510(7503), 121–125 (2014). https://doi.org/10.1038/nature13306
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