A bioinspired sulfur–Fe–heme nanozyme with selective peroxidase-like activity for enhanced tumor chemotherapy

Shuaibing Zhang, Xuejiao J. Gao, Yuanjie Ma, Kexu Song, Mengyue Ge, Saiyu Ma, Lirong Zhang, Ye Yuan, Wei Jiang, Zhenzhen Wu, Lizeng Gao (), Xiyun Yan () and Bing Jiang ()
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Shuaibing Zhang: Zhengzhou University
Xuejiao J. Gao: Jiangxi Normal University
Yuanjie Ma: Jiangxi Normal University
Kexu Song: Zhengzhou University
Mengyue Ge: Zhengzhou University
Saiyu Ma: Zhengzhou University
Lirong Zhang: Zhengzhou University
Ye Yuan: Zhengzhou University
Wei Jiang: Zhengzhou University
Zhenzhen Wu: Chinese Academy of Sciences
Lizeng Gao: Zhengzhou University
Xiyun Yan: Zhengzhou University
Bing Jiang: Zhengzhou University

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: Abstract Iron-based nanozymes, recognized for their biocompatibility and peroxidase-like activities, hold promise as catalysts in tumor therapy. However, their concurrent catalase-like activity undermines therapeutic efficacy by converting hydrogen peroxide in tumor tissues into oxygen, thus diminishing hydroxyl radical production. Addressing this challenge, this study introduces the hemin–cysteine–Fe (HCFe) nanozyme, which exhibits exclusive peroxidase-like activity. Constructed through a supramolecular assembly approach involving Fmoc-l-cysteine, heme, and Fe²⁺ coordination, HCFe distinctly incorporates heme and [Fe–S] within its active center. Sulfur coordination to the central Fe atom of Hemin is crucial in modulating the catalytic preference of the HCFe nanozyme towards peroxidase-like activity. This unique mechanism distinguishes HCFe from other bifunctional iron-based nanozymes, enhancing its catalytic selectivity even beyond that of natural peroxidases. This selective activity allows HCFe to significantly elevate ROS production and exert cytotoxic effects, especially against cisplatin-resistant esophageal squamous cell carcinoma (ESCC) cells and their xenografts in female mice when combined with cisplatin. These findings underscore HCFe’s potential as a crucial component in multimodal cancer therapy, notably in augmenting chemotherapy efficacy.

Date: 2024
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DOI: 10.1038/s41467-024-54868-w

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