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A Supramolecular Thermal Switch for Precision Pyroptosis via Host-Guest Recognition and Electrostatic Interactions
Dan Wu1, Jie Zhou1, Yibin Cao1
1State Key Laboratory of Advanced Separation Membrane Materials, Zhejiang Key Laboratory of Advanced Polymer Materials Modification and Application Technology, College of Materials Science and Engineering, Zhejiang University of Technology, Hangzhou, P. R. China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 20, 2026
Summary
Engineered supramolecular system precisely triggers pyroptosis for enhanced antitumor immunity. This approach overcomes limitations of conventional inducers, offering a novel strategy for cancer immunotherapy.
Area of Science:
- Biomedical Engineering
- Immunology
- Materials Science
Background:
- Gasdermin (GSDM)-mediated pyroptosis is crucial for antitumor immunity but faces challenges in precise induction.
- Conventional pyroptosis inducers exhibit rigidity, inefficiency, and systemic toxicity, limiting their therapeutic application.
Purpose of the Study:
- To engineer a supramolecular thermal switch for programmable and precise pyroptosis induction.
- To develop a novel system for potentiating cancer immunotherapy by overcoming limitations of existing methods.
Main Methods:
- Stabilization of triiodide ions (I3-) within β-cyclodextrin (β-CD) and nucleation of CaCO3 matrix for controlled ion release.
- Utilizing a pH-responsive CaCO3 matrix and a near-infrared (NIR) laser-activated boron dipyrromethene (BODIPY) thermal switch.
- Inducing pyroptosis via synergistic effects of released I3-, Ca2+, and intracellular oxidative stress.
Main Results:
- The supramolecular system enabled site-specific release of I3- and Ca2+ in the acidic tumor microenvironment.
- NIR laser activation triggered I3- conversion to I2, leading to oxidative stress and calcium dysregulation.
- Combined Ca2+ burst and pyroptosis induction via caspase-3/GSDME pathway effectively inhibited tumor growth and metastasis.
Conclusions:
- The engineered supramolecular thermal switch provides a precise and programmable platform for pyroptosis induction.
- This strategy enhances antitumor immunity by connecting innate and adaptive immune responses.
- The approach holds promise for developing advanced cancer immunotherapies.
