biostudies-literatureUnknown56Sun SChemoresistance and immunosuppression serve as major obstacles that compromise the therapeutic efficacy of chemoimmunotherapy. Herein, we reported a novel chemoimmunotherapy strategy employing metal fluoride to modulate Wnt/β-catenin signaling, effectively remodeling treatment resistance and eliciting pyroptosis-mediated immune activation. Through systematic screening of various nonmetallic anions (F^-, Cl^-, Br^-, I^-, CO₃ ^2-, PO₄ ^3-, S^2-, and Se^2-), we identified F^- as an effective inhibitor of β-catenin expression and tumor stemness. The synergistic combination of F^- with chemotherapy significantly attenuated tumor stemness and enhanced treatment efficacy. We fBioactive materials248-259https://www.ebi.ac.uk/biostudies/studies/S-EPMC12590230biostudies-literatureMetal fluoride nanoregulators reverse therapeutic resistance via stemness remodeling to trigger pyroptosis for chemoimmunotherapy.PMC12590230Yang NSun SWang DNie JCheng LZhang LSun XJin YfalseMetal fluoride nanoregulators reverse therapeutic resistance via stemness remodeling to trigger pyroptosis for chemoimmunotherapy.Chemoresistance and immunosuppression serve as major obstacles that compromise the therapeutic efficacy of chemoimmunotherapy. Herein, we reported a novel chemoimmunotherapy strategy employing metal fluoride to modulate Wnt/β-catenin signaling, effectively remodeling treatment resistance and eliciting pyroptosis-mediated immune activation. Through systematic screening of various nonmetallic anions (F^-, Cl^-, Br^-, I^-, CO₃ ^2-, PO₄ ^3-, S^2-, and Se^2-), we identified F^- as an effective inhibitor of β-catenin expression and tumor stemness. The synergistic combination of F^- with chemotherapy significantly attenuated tumor stemness and enhanced treatment efficacy. We f2026-01-01T00:00:00Z2026 Feb2026-06-05T14:44:40.091Z2026-05-18T03:08:19.496ZS-EPMC125902304121157710.1016/j.bioactmat.2025.10.011