Sodium Chloride

Sodium chloride, through its sodium ion component, acts as a key modulator of immune cell function via multiple molecular mechanisms. In CD8+ T cells, elevated sodium enhances the activation state and effector functions by upregulating Na+/K+-ATPase activity, leading to membrane hyperpolarization, which magnifies the electromotive force for T cell receptor-induced calcium influx and downstream signaling. In CD4+ T cells, sodium promotes Th17 cell differentiation through the serum glucocorticoid kinase 1 (SGK1) pathway, which is crucial for interleukin-23 receptor expression.
Sodium also modulates regulatory T cell function and alters macrophage polarization, shifting them towards a pro-inflammatory phenotype. In the skin and other tissues, sodium accumulates in the interstitium, creating hypertonic microenvironments that influence local immune responses. The effects of sodium on immune cells are both direct, through activation of tonicity-responsive enhancer-binding protein (NFAT5) and SGK1 signaling, and indirect, via modulation of the gut microbiome.

Fig. 1 Salt promotes activation of pro-inflammatory macrophages. (Wilck N.; et al. 2019)

Sodium chloride nanoparticles were developed as a novel radiosensitizer for cancer therapy. Unlike conventional radiosensitizers that rely on high-Z effects, SCNPs potentiate radiation-induced cellular damage by elevating intracellular sodium levels, which reverses the sodium/calcium exchanger and triggers calcium influx. This calcium surge not only amplifies radiation-induced cancer cell death but also activates the cGAS-STING pathway, leading to type I interferon production. In syngeneic head and neck cancer models, SCNPs combined with radiation significantly improved tumor control and long-term survival without detectable toxicity. Mechanistic studies revealed that the therapeutic benefits are largely immune-mediated, evidenced by enhanced dendritic cell maturation and increased tumor infiltration of T cells.

Fig. 2 Mechanism of FA-SCNPs-induced calcium influx. (Zhan S.; et al. 2025)