Sodium Chloride Nanoparticles as Radiosensitizers

Previous studies have demonstrated that SCNPs can enter cells through endocytosis and disrupt osmotic balance by releasing sodium and chloride ions. This process leads to cancer cell death. It's speculated that the SCNPs might affect the levels of other ions in the cells and have a significant impact on the redox balance. The research suggests that combining SCNPs with radiation therapy could enhance the effectiveness of the treatment. Radiation therapy works by ionizing molecules, especially water, to produce radicals that damage biomolecules like DNA. SCNPs might enhance this effect by promoting the production of reactive oxygen species (ROS).<br/><br/>In particular, we are interested in exploring SCNPs as a radiosensitizer for head and neck squamous cell carcinoma (HNSCC). HNSCC, a significant and increasingly common malignancy, often requires treatment through surgery or radiotherapy. However, these treatments have limitations, including toxicity and a high risk of recurrence. Combining chemotherapy with radiotherapy increases efficacy but also the risk of systemic toxicities. SCNPs are considered as a potential new treatment modality that could improve efficacy without adding toxicity.<br/><br/>In this study, we synthesized and characterized folate-conjugated sodium chloride nanoparticles (SCNPs@folate) and explored their potential as radiation sensitizers in HNSCC. Our results showed that the nanoparticles exhibited proficient cellular uptake and increased intracellular levels of sodium and chloride. Interestingly, the increase in sodium levels also causes calcium influx through the NCX, triggering an increase in ROS. We found that the ROS-promoting effect works in tandem with IR, leading to GSH depletion, resulting in DNA and lipid damage, and ultimately cell death. Our in vitro results showed that there is a synergistic effect between SCNPs@folate and IR. In vivo studies showed that intratumorally injection of SCNPs@folate combined with irradiation resulted in a significant improvement in tumor growth inhibition compared to IR alone and a higher percentage of tumor-free mice. Taken together, our studies suggest a great potential of SCNPs@folate as a radiosensitizer in HNSCC.