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Mitochondria-Targeted Zwitterionic Nanogels Trigger Photopyroptosis for Enhanced Cancer Therapy.
Yuxin Huang1, Shuting Mai1, Shaoqi Sheng1
1State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, P. R. China.
Small (Weinheim an Der Bergstrasse, Germany)
|May 17, 2026
Summary
This study introduces zwitterionic nanogels for precise photopyroptosis cancer therapy. The nanogels target mitochondria, triggering cell death with minimal toxicity and achieving 99.3% tumor inhibition.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Inducing pyroptosis for cancer treatment is challenging due to control requirements.
- Mitochondrial targeting offers a precise approach for cancer therapy.
Purpose of the Study:
- To develop a zwitterionic nanogel platform for precise photopyroptosis induction.
- To achieve subcellular mitochondrial targeting for enhanced cancer therapy.
Main Methods:
- Synthesized poly(N-oxide dimethylaminoethyl methacrylate) (PODMMA) zwitterionic nanogels.
- Evaluated in vitro mitochondrial accumulation and drug delivery.
- Assessed in vivo tumor inhibition and systemic toxicity after laser irradiation.
Main Results:
- PODMMA nanogels demonstrated prolonged circulation, selective mitochondrial localization, and tumor accumulation.
- Phototriggered reactive oxygen species (ROS) amplification activated the pyroptosis pathway (caspase-3/GSDME).
- Achieved 99.3% tumor inhibition with negligible systemic toxicity.
Conclusions:
- Zwitterionic nanogels provide a versatile platform for subcellular-targeted photopyroptosis.
- This strategy enables precise cancer therapy with high efficacy and safety.
- Mitochondrial-targeted photopyroptosis represents a promising approach for precision oncology.
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