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Nanotherapeutic System with Effective Microwave Sensitization and Pyroptosis Programming Enable Synergistic
Hao Deng1,2,3, Jinliang Huang1,2, Ning Gao1
1Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Biomaterials Research
|July 9, 2025
Summary
This study introduces Mn-ZrMOF@DAC, a novel nanoparticle therapy that combines microwave treatment with decitabine to induce pyroptosis and enhance antitumor immunity for bladder cancer, improving immunotherapy efficacy.
Area of Science:
- Biomedical Engineering
- Cancer Therapy
- Immunology
Background:
- Advanced bladder cancer prognosis is poor, with limited response to current immunotherapies.
- Conventional microwave therapy has limitations in efficacy and immune stimulation.
- Pyroptosis induction is a promising strategy to enhance anti-tumor immunity.
Purpose of the Study:
- To develop a novel microwave-sensitized nanoparticle (Mn-ZrMOF@DAC) loaded with decitabine for bladder cancer treatment.
- To investigate the potential of this therapy to enhance microwave treatment efficacy and induce pyroptosis.
- To evaluate the combined effect of Mn-ZrMOF@DAC, microwave therapy, and anti-PD-1 immunotherapy in vivo.
Main Methods:
- Development of Mn-ZrMOF@DAC nanoparticles encapsulating decitabine.
- In vitro assessment of nanoparticle-mediated thermal and oxidative damage to cancer cells.
- Evaluation of pyroptosis induction via GSDME upregulation.
- In vivo studies in mice combining nanoparticle treatment, microwave radiation, and anti-PD-1 therapy.
Main Results:
- Mn-ZrMOF@DAC enhanced microwave thermal therapy, generating reactive oxygen species and causing cancer cell damage.
- The treatment significantly upregulated GSDME, a key pyroptosis protein, leading to increased pyroptotic cell death.
- In vivo experiments showed potent anti-tumor effects and enhanced efficacy of anti-PD-1 immunotherapy.
Conclusions:
- Mn-ZrMOF@DAC combined with microwave therapy effectively treats bladder cancer by inducing pyroptosis.
- This approach activates antitumor immunity, overcoming limitations of conventional microwave therapy.
- The developed therapy offers a promising strategy to enhance immunotherapy for advanced bladder cancer.
