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Single Atom Ru Doped CuTi Nanozyme with Precisely Programmed Cascade Catalysis for Amplified Oral Cancer Therapy
Guanmeng Zhang1, Ludan Zhang2, Zuhao Shi3
1Department of General Dentistry II, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.
A novel nanozyme platform enhances chemodynamic therapy (CDT) for oral cancer by precisely controlling catalytic reactions. This approach overcomes CDT limitations, amplifying tumor cell death and improving treatment efficacy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Oral squamous cell carcinoma (OSCC) lacks effective, low-toxicity treatments.
- Chemodynamic therapy (CDT) shows promise but is limited by low H2O2 levels, high glutathione (GSH), and single cell death pathways.
Purpose of the Study:
- To develop a programmable nanozyme platform to overcome CDT limitations for OSCC treatment.
- To engineer a Ru-CuTi-LDH nanozyme with tunable catalytic functions for enhanced cancer therapy.
Main Methods:
- Synthesized Ru single atoms anchored on CuTi layered double hydroxide (Ru CuTi-LDH) nanozyme.
- Utilized Ru sites for superoxide dismutase (SOD)-like activity and controlled peroxidase (POD), catalase (CAT), and glutathione peroxidase (GPx) functions.
- Orchestrated cascade reactions involving superoxide radical conversion, Fenton-like reactions, GSH depletion, and O2 generation.
Main Results:
- The Ru CuTi-LDH nanozyme amplified oxidative damage and sensitized OSCC cells to cuproptosis.
- Triggered endoplasmic reticulum (ER) stress, activating paraptosis, leading to three simultaneous cell death pathways.
- Achieved 84.7% tumor inhibition and prolonged survival in an orthotopic OSCC model.
Conclusions:
- The developed nanozyme platform effectively addresses fundamental CDT limitations through atomic-level tunable cascade catalysis.
- This strategy significantly enhances therapeutic efficacy for OSCC by inducing multiple cell death pathways and overcoming the tumor microenvironment.
- Presents a promising chemical strategy for advanced cancer therapy.

