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Zinc-Doped Calcium Phosphate Nanoagonists Amplifies cGAS-STING Signaling for Boosting Pyroptosis-Induced Cancer
Bangliu Yang1, Xinyu Li1, Mingyue Zhang1
1Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
Journal of Functional Biomaterials
|June 25, 2026
Summary
This study introduces ZCPDM, a novel nanodrug delivery system that combines chemotherapy and immunotherapy. ZCPDM effectively targets cancer cells, enhancing anti-tumor immunity and reducing recurrence with good biosafety.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Chemotherapy and immunotherapy offer synergistic anti-cancer benefits but face challenges with side effects and low immune activation.
- Developing targeted drug delivery systems is crucial for improving cancer treatment efficacy and safety.
Purpose of the Study:
- To develop a novel nanodrug delivery system (ZCPDM) for synergistic chemo-immunotherapy.
- To investigate the mechanisms of ZCPDM-mediated tumor cell targeting, drug release, and immune activation.
Main Methods:
- Fabrication of zinc-doped calcium phosphate (ZCP) nanocarriers for doxorubicin (DOX) delivery.
- Encapsulation of 4T1 breast cancer cell proteins to create the ZCPDM system for homologous targeting.
- In vitro and in vivo evaluation of ZCPDM's anti-tumor efficacy, mechanism of action (ROS generation, DNA damage, cGAS-STING pathway activation, pyroptosis), and biosafety.
Main Results:
- ZCPDM demonstrated specific tumor cell targeting and intracellular release of DOX, Zn2+, and Ca2+.
- DOX induced apoptosis and elevated reactive oxygen species (ROS), leading to DNA damage and chromosomal fragment release.
- The released DNA fragments and Zn2+ activated the cGAS-STING pathway, triggering pyroptosis and enhancing immune cell recognition and clearance of tumor cells.
- ZCPDM exhibited robust anti-tumor performance, suppressed tumor recurrence, and showed good biosafety in tumor-bearing mice.
Conclusions:
- ZCPDM effectively combines chemotherapy and immunotherapy through dual mechanisms: DOX-induced apoptosis and pyroptosis activation via the cGAS-STING pathway.
- This targeted nanodrug delivery system offers a promising strategy for safe and synergistic chemo-immunotherapy, showing potential for cancer treatment and reducing tumor recurrence.
