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.
None:
Pyroptosis is a promising strategy for tumor immunotherapy, but nanomaterial-based pyroptosis inducers remain underexplored. Here, we developed a pH-responsive calcium nanomodulator by loading curcumin onto ultrathin Ca/Al layered double hydroxide nanosheets (LDH-CUR). LDH-CUR induces pyroptosis via mitochondrial calcium overload. Upon internalization by tumor cells, it degrades in acidic environments, releasing calcium ions while curcumin blocks calcium efflux, leading to calcium surges. This triggers reactive oxygen species production, cytochrome C release, and caspase-3 activation. Caspase-3 cleaves gasdermin E (GSDME), forming transmembrane pores and inducing pyroptosis. Pyroptosis releases inflammatory molecules, activating robust adaptive immunity to target primary tumors and suppress metastases. LDH-CUR demonstrates a novel approach to combining pyroptosis induction with immunotherapy, offering potential for nanomaterial-based cancer treatments.
