Calcium ion nanomodulators induce pyroptosis for tumor immunotherapy
Fenggang Qi1,2, Yuedong Guo3, Yangxian Xu4
1State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Ding-Xi Road, Shanghai 200050, P. R. China. huping@mail.sic.ac.cn.
Nanoscale
|October 29, 2025
Summary
This study introduces a novel nanomaterial that triggers pyroptosis (a form of programmed cell death) in cancer cells. This approach enhances tumor immunotherapy by activating the immune system to fight primary tumors and metastases.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunotherapy
Background:
- Pyroptosis is a promising immunotherapy strategy for tumors.
- Nanomaterial-based pyroptosis inducers are underexplored.
- Developing novel nanomaterials for cancer treatment is crucial.
Purpose of the Study:
- To develop a pH-responsive calcium nanomodulator for pyroptosis induction.
- To investigate the mechanism of pyroptosis induction by the nanomodulator.
- To evaluate the potential of the nanomodulator in tumor immunotherapy.
Main Methods:
- Loading curcumin onto Ca/Al layered double hydroxide nanosheets (LDH-CUR).
- Investigating pH-responsive degradation and calcium ion release.
- Analyzing pyroptosis induction via mitochondrial calcium overload, ROS production, and caspase-3 activation.
- Assessing the immune response and anti-tumor effects in vivo.
Main Results:
- LDH-CUR effectively induces pyroptosis through mitochondrial calcium overload in acidic tumor environments.
- Curcumin release and calcium ion accumulation trigger reactive oxygen species and caspase-3 activation.
- Caspase-3 cleavage of gasdermin E (GSDME) leads to pyroptosis and inflammatory molecule release.
- Pyroptosis activates adaptive immunity, targeting primary tumors and suppressing metastases.
Conclusions:
- LDH-CUR offers a novel nanomaterial-based approach for pyroptosis induction and cancer immunotherapy.
- This strategy combines pyroptosis with adaptive immunity for enhanced anti-tumor efficacy.
- The developed nanomodulator shows potential for future clinical applications in cancer treatment.
