biostudies-literatureZhan SNIDCR NIH HHSNCATS NIH HHSNCI NIH HHS14032-14042https://www.ebi.ac.uk/biostudies/studies/S-EPMC12464967biostudies-literatureUnknown25(38)This study investigates sodium chloride nanoparticles (SCNPs) as radiosensitizers. In contrast to conventional radiosensitizers that rely on high-Z effects or DNA-targeted mechanisms, SCNPs potentiate radiation-induced cellular damage by perturbing ion homeostasis. Importantly, SCNPs by elevating intracellular sodium levels reverse the sodium/calcium exchanger (NCX), leading to calcium influx. This calcium surge not only amplifies radiation-induced cancer cell death but also activates the cGAS-STING pathway, leading to the production of type I interferons. In syngeneic head and neck cancer models, SCNPs significantly improve tumor control and long-term survival in combination with radiation, without inducing detectable toxicity. Mechanistic studies reveal that these therapeutic benefits arNano lettersSodium Chloride Nanoparticles Potentiate Radiation Therapy by Disrupting Osmolarity Balance and Enhancing Antitumor Immunity.PMC12464967R01 DE033433R01 CA247769R01 DE028351R01 CA257851UL1 TR002378P30 CA138292R01 DE033691Lai XYang WZheng YLi JYao YFeng ZZhan SXie JPatel SBTeng YfalseSodium Chloride Nanoparticles Potentiate Radiation Therapy by Disrupting Osmolarity Balance and Enhancing Antitumor Immunity.This study investigates sodium chloride nanoparticles (SCNPs) as radiosensitizers. In contrast to conventional radiosensitizers that rely on high-Z effects or DNA-targeted mechanisms, SCNPs potentiate radiation-induced cellular damage by perturbing ion homeostasis. Importantly, SCNPs by elevating intracellular sodium levels reverse the sodium/calcium exchanger (NCX), leading to calcium influx. This calcium surge not only amplifies radiation-induced cancer cell death but also activates the cGAS-STING pathway, leading to the production of type I interferons. In syngeneic head and neck cancer models, SCNPs significantly improve tumor control and long-term survival in combination with radiation, without inducing detectable toxicity. Mechanistic studies reveal that these therapeutic benefits ar2025-01-01T00:00:00Z2025 Sep2026-06-03T21:16:39.956Z2026-05-01T03:10:52.879ZS-EPMC124649674094765110.1021/acs.nanolett.5c03022