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Updated: Jan 14, 2026
Electrochemotherapy of Tumours
Published on: December 15, 2008
Electro-activated nanozyme for in situ tumor vaccination: Synergistic multi-enzyme catalysis and electrodynamic
Bowen Dai1, Haoyu Yu2, Tao Zhang2
1Department of Oral and Maxillofacial Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, China.
Abstract:
Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis and limited treatment options. To address the challenges of conventional therapy resistance, antioxidant defence, and immune evasion, we developed a multifunctional nanozyme platform, MIL-100(Fe)@Pt@R837@HA (HMPR), that integrates electrodynamic therapy (EDT), chemodynamic therapy, and immunotherapy. The multi-enzyme activities of HMPR allow for the oxygen generation, hydroxyl radicals production, and glutathione depletion, thereby alleviating hypoxia and triggering both apoptosis and ferroptosis. Under electrical stimulation, HMPR promotes significant production of reactive oxygen species via Pt-mediated EDT to amplify ferroptosis and immunogenic cell death (ICD). In addition, the tumor-specific GSH level triggers the release of the immune adjuvant R837. The potent ICD effect, combined with the sustained release of the adjuvant R837, endows the nanozyme HMPR with the characteristics of an in situ "tumor vaccine", continuously promoting dendritic cell maturation, activating T cell-mediated immunity, and establishing long-term immunological memory to prevent tumor recurrence and inhibition of distant tumor growth. This cascade effect reprograms the immunosuppressive tumor microenvironment into an immunostimulatory one, significantly enhancing the efficacy of PD-1 blockade. Our study provides a powerful electro-enhanced nanozyme-immune synergistic strategy for OSCC and offers a flexible platform adaptable to other solid tumors.
Insights
A novel nanozyme platform (HMPR) combines therapies to treat oral cancer by triggering cell death and activating the immune system. This approach enhances anti-tumor immunity and PD-1 blockade efficacy, offering a new strategy for oral squamous cell carcinoma.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Oral squamous cell carcinoma (OSCC) presents significant therapeutic challenges due to resistance, immune evasion, and poor prognosis.
- Existing treatments for OSCC are limited and often ineffective against aggressive forms of the disease.
Purpose of the Study:
- To develop a multifunctional nanozyme platform (HMPR) integrating electrodynamic therapy (EDT), chemodynamic therapy, and immunotherapy for OSCC treatment.
- To investigate HMPR's ability to overcome therapeutic resistance, combat immune evasion, and enhance anti-tumor immunity.
Main Methods:
- Fabrication of MIL-100(Fe)@Pt@R837@HA (HMPR) nanozyme.
- Evaluation of HMPR's multi-enzyme activities including oxygen generation, hydroxyl radical production, and glutathione depletion.
- Assessment of HMPR-mediated apoptosis, ferroptosis, and immunogenic cell death (ICD) under electrical stimulation.
- Analysis of HMPR's effect on the tumor microenvironment, immune cell activation, and efficacy of PD-1 blockade.
Main Results:
- HMPR alleviates tumor hypoxia and induces apoptosis and ferroptosis via multi-enzyme activities.
- Electrical stimulation of HMPR amplifies ferroptosis and ICD through enhanced reactive oxygen species production.
- HMPR acts as an in situ tumor vaccine, promoting dendritic cell maturation and T cell immunity, establishing long-term memory.
- HMPR reprograms the immunosuppressive tumor microenvironment, significantly boosting PD-1 blockade efficacy.
Conclusions:
- The HMPR nanozyme platform offers a potent electro-enhanced synergistic strategy for OSCC treatment.
- This approach effectively combines multiple therapeutic modalities to enhance anti-tumor immune responses.
- The HMPR platform demonstrates potential adaptability for treating other solid tumors.
