Ultrasmall metal alloy nanozymes mimicking neutrophil enzymatic cascades for tumor catalytic therapy

Xiangqin Meng, Huizhen Fan, Lei Chen, Jiuyang He, Chaoyi Hong, Jiaying Xie, Yinyin Hou, Kaidi Wang, Xingfa Gao, Lizeng Gao, Xiyun Yan () and Kelong Fan ()
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Xiangqin Meng: Chinese Academy of Sciences
Huizhen Fan: Chinese Academy of Sciences
Lei Chen: Chinese Academy of Sciences
Jiuyang He: Beijing Institute of Technology
Chaoyi Hong: Chinese Academy of Sciences
Jiaying Xie: Chinese Academy of Sciences
Yinyin Hou: Chinese Academy of Sciences
Kaidi Wang: Chinese Academy of Sciences
Xingfa Gao: National Center for Nanoscience and Technology
Lizeng Gao: Chinese Academy of Sciences
Xiyun Yan: Chinese Academy of Sciences
Kelong Fan: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract Developing strategies that emulate the killing mechanism of neutrophils, which involves the enzymatic cascade of superoxide dismutase (SOD) and myeloperoxidase (MPO), shows potential as a viable approach for cancer therapy. Nonetheless, utilizing natural enzymes as therapeutics is hindered by various challenges. While nanozymes have emerged for cancer treatment, developing SOD-MPO cascade in one nanozyme remains a challenge. Here, we develop nanozymes possessing both SOD- and MPO-like activities through alloying Au and Pd, which exhibits the highest cascade activity when the ratio of Au and Pd is 1:3, attributing to the high d-band center and adsorption energy for superoxide anions, as determined through theoretical calculations. The Au1Pd3 alloy nanozymes exhibit excellent tumor therapeutic performance and safety in female tumor-bearing mice, with safety attributed to their tumor-specific killing ability and renal clearance ability caused by ultrasmall size. Together, this work develops ultrasmall AuPd alloy nanozymes that mimic neutrophil enzymatic cascades for catalytic treatment of tumors.

Date: 2024
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DOI: 10.1038/s41467-024-45668-3

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