Radionuclide-labeled oxygen-self-supplying calcium reservoir for high-efficiency radioimmunotherapy via synergistic pyroptosis activation and PD-L1 downregulation.

Authors

Lin Liu, Kaiyan Huang, Hanjing Guo, Linping He, Xin Wang, Chao Wang, Jianqing Lin, Naihan Huang, Weibing Miao

Published in

Journal of nanobiotechnology. Jun 19, 2026. Epub Jun 19, 2026.

Abstract

Internal radiation therapy is an irreplaceable modality for local tumor treatment, offering high-effective radiotherapy while sparing surrounding healthy tissues. However, current clinical non-biodegradable radionuclide implants suffer from permanent retention risks and limited efficacy against distal tumors due to inadequate immune activation. Herein, we engineered a biodegradable radionuclide-labeled oxygen-self-supplying calcium reservoir (¹³¹I@CaO₂), fabricated through biomimetic mineralization followed by chloramine-T mediated ¹³¹I-radiolabeling, for high-efficiency internal-radioimmunotherapy. ¹³¹I@CaO₂ effectively enhances the internalization of ¹³¹I to improve internal-radiotherapy and exhibits pH-responsive biodegradability, remaining stable under physiological condition while progressively degrading in tumor microenvironment to release H₂O₂, O₂ and Ca²⁺. These bioactivators synergistically enhance ¹³¹I-induced internal-radioimmunotherapy through both radiosensitization and immune activation: H₂O₂ and O₂ boost ¹³¹I-induced ROS generation while Ca²⁺ disrupted mitochondrial respiration to reduce oxygen consumption and ATP production (suppressing Ca²⁺ pump activity), creating a positive feedback loop of oxygen supply and ion overload, thereby achieving radiosensitization; Concurrently, O₂ alleviates tumor hypoxia to downregulate PD-L1 expression and Ca²⁺ overload activates dual pyroptosis pathways, establishing a robust immunogenic microenvironment. As a result, ¹³¹I@CaO₂ effectively eliminates both primary and distant tumors by activating immune cells. This study simultaneously resolves the long-term retention risks of non-biodegradable radionuclide and the dichotomy between local radiotherapy and comprehensive immune modulation.

PMID:
42321813
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.

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