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  3. Interfacial strong interaction-enabling cascade nanozymes for apoptosis-ferroptosis synergistic therapy

Interfacial strong interaction-enabling cascade nanozymes for apoptosis-ferroptosis synergistic therapy

  • J Colloid Interface Sci. 2024 Jan;653(Pt A):20-29. doi: 10.1016/j.jcis.2023.09.036.
Lineng Wei 1,  Ziyu Wang 1,  Xiuxin Lu 1,  Jingqi Chen 1,  Yujie Zhai 1,  Qinghua Huang 2,  Shenglin Pei 3,  Yan Liu 4,  Weiqing Zhang 5
Affiliations

Affiliations

  • 1 Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China.
  • 2 Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China; Department of Breast Surgery, Wuzhou Red Cross Hospital, Wuzhou 543000, China. Electronic address: [email protected].
  • 3 Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China.
  • 4 Department of Breast, Bone and Soft Tissue Oncology, Guangxi Medical University Cancer Hospital, Nanning, Nanning 530021, China; Laboratory of Breast Cancer Diagnosis and Treatment Research of Guangxi Department of Education, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China. Electronic address: [email protected].
  • 5 Department of Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, China. Electronic address: [email protected].
PMID: 37708728 DOI: 10.1016/j.jcis.2023.09.036
Abstract

Noble metal nanozymes are promising therapeutic agents due to their good ability of Reactive Oxygen Species generation in response to the tumor microenvironment (TME). Achieving optimal performance of noble metal nanozymes at a minimum dosage is crucial due to potential systemic biotoxicity. In this study, we report the successful anchoring of Ir nanoclusters on Co(OH)2 nanosheets with an Ir content of 6.2 wt% (denoted as Ir6.2-Co(OH)2), which exhibits remarkable peroxidase (POD)- and catalase (CAT)-like activities. The strong electronic interaction at the Ir-O-Co interface endows Glutathione Peroxidase (GSH-Px)-like activity to the composite, ensuring efficient generation of Reactive Oxygen Species (ROS) and deactivation of Glutathione Peroxidase 4 (GPX4) by supplementing hydrogen peroxide (H2O2) and depleting glutathione (GSH). Both in vitro and in vivo evaluations demonstrate that Ir6.2-Co(OH)2 nanozymes significantly enhance antitumor efficacy through apoptosis-ferroptosis synergistic therapy. This study highlights the tremendous potential of leveraging strong electronic interactions between noble metals and oxides for modulating enzyme-like activities towards high-efficiency synergistic therapies.

Keywords

Antitumor therapy; Apoptosis; Cascade nanozymes; Ferroptosis; Interfacial interaction.

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