Authors
Qian-Sheng Lai, Yan-Ling Chen, Xin-Xiong Li, Peng Xu, Shou-Tian Zheng
Published in
Angewandte Chemie (International ed. in English). Oct 29, 2026. Epub Oct 29, 2026.
Abstract
Cancer immunotherapy is limited by insufficient immunomodulatory efficacy and systemic toxicity. This study reports a giant silver cluster-incorporated polyoxoniobate (PONb), K6Na21H39{Ag30Cl4(SeO3)4@(SiNb18O54)6}·96H2O (1), as a potent immunotherapeutic agent. 1 features a unique core-shell architecture, comprising a silver cluster core [Ag30Cl4(SeO3)4]18+ and a shell of six [SiNb18O54]14- polyanions. Notably, 1 contains the largest silver cluster (30 Ag+) in a molecular PONb with solubility and biocompatibility under physiological conditions to date. In vitro, 1 exhibits potent cytotoxicity against mouse colorectal carcinoma cells with an IC50 of 0.11 µM, triggering immunogenic cell death (ICD). Additionally, it induces polarization of macrophages to the antitumor M1-phenotype. In vivo, it outperforms doxorubicin (DOX) in suppressing tumor growth, with 1 achieving 90.63% tumor inhibition at 5 mg/kg (0.23 µmol/kg). Unlike DOX-induced immunosuppression and hepatic toxicity, 1 robustly activates antitumor immune response via an ROS-dependent mechanism by promoting T cell priming in the tumor-draining lymph node and effector T cell infiltration into tumors, without impairing organ functions. Moreover, 1 converts tumor-associated macrophages (TAMs) from the protumorogenic M2-phenotype to the antitumor M1-phenotype, further reprogramming the immune microenvironment in tumor tissues. This study validates PONbs as a promising class of immunotherapeutics, bridging structural innovation in inorganic chemistry with improved cancer immunotherapy.
PMID:
42952413
Bibliographic data and abstract were imported from PubMed on 29 Oct 2026.
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