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

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 (As3+ and As5+), 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.