A biomimetic arsenic-based nanozyme enhances dual epigenetic regulation to improve the efficacy of immunotherapy for acute myeloid leukaemia.

Chang, Aqian; Peng, Hulinyue; Chen, Yang; Zhang, Huizhong; Xu, Xiaohan; Zhang, Ke; Yang, Jingwen; Li, Wenjing et al. · Biomaterials · 2026

basic_science · Level V

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Abstract

Aberrant epigenetic modifications in acute myeloid leukaemia (AML) limit immunotherapeutic efficacy. Arsenic ions are capable of undergoing valence transformation in organisms, exhibit favourable enzyme-mimetic activity, and thereby play a crucial role in enhancing dual epigenetic regulation. Therefore, to achieve potent epigenetic regulation, in this study, a biomimetic arsenic-based nanozyme (As/ZIF-8@M) that exhibits leukaemia cell recognition and phagocytosis capabilities, as well as bone marrow homing effects, was engineered. Within AML cells, this nanozyme exerted peroxidase (POD)-like and glutathione oxidase (GSHOx)-like activities through the valence state conversion of arsenic (As<sup>3+</sup> and As<sup>5+</sup>), thereby achieving potent regulation of DNA methylation and arginine methylation. This further activated the cGAS-STING pathway, leading to reversal of the immunosuppressive microenvironment in AML, increased PD-L1 blockade efficacy, and subsequent improvements in immunotherapy efficacy for leukaemia. This study presents the first biomimetic arsenic-based nanozyme leveraging catalysis to remodel the AML microenvironment, thereby enhancing dual epigenetic regulation. This innovative strategy holds significant promise for improving the efficacy of immunotherapy for leukaemia.