Presentation description

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally. Approximately 50% of advanced-stage patients experience poor long-term survival rates due to minimal effective treatment options and/or resistance to chemo- and radiotherapy.
Preclinical studies show that methylselenocysteine (MSC), an organic selenium (Se) compound, can restore chemotherapy sensitivity in tumor cells via reactive oxygen species (ROS) production and impairment of antioxidant mechanisms. However, the required effective dose of MSC causes systemic toxicity. With modifications to ensure safety, MSC could offer substantial therapeutic benefits. Thus, we developed a selenium-functionalized hyaluronic acid compound (sHASe 011) that targets tumor cells. Hyaluronic acid (HA) is a natural glycosaminoglycan and ligand of cluster differentiation 44, a common cell surface receptor found in HNSCC cells. This design enables targeted delivery to the HNSCC tumor microenvironment to induce redox-based mechanisms that reduce therapy resistance, tumor cell survival, and systemic side effects.
MSC was covalently conjugated to low molecular weight HA through carbodiimide-mediated coupling. Proton nuclear magnetic resonance, inductively coupled plasma mass spectrometry, and gel permeation chromatography were used to structurally characterize the conjugate. To evaluate selective cytotoxicity, cell viability was assessed following sHASe 011 incubation in both healthy (human umbilical vein endothelial cells; HUVECs) and pharyngeal tumor (FaDu) cells under normal and oxidative stress induction with tert-butyl hydroperoxide. No significant difference between HUVEC and FaDu cell viability was observed when incubated with sHASe 011 compared to controls. However, under oxidative stress, a significant dose-dependent reduction in FaDu cell viability was detected, suggesting that sHASe 011 exerts ROS-sensitizing effects on oxidative stress resistance in HNSCC cells. Future studies are ongoing to test sHASe 011's ability to decrease cell viability in chemotherapy-resistant HNSCC cell lines.