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Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and
therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis,
resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia
(mNPHT) is a promising therapy for hypoxic tumors because nanoparticles (NP) can be directly injected into, or targeted to, hypoxic tumor cells and exposed to alternating magnetic fields (AMF) to induce hyperthermia. Magnetic NPHT can
improve therapeutic effectiveness by two modes of action: 1) direct killing of hypoxic tumor cells; and 2) increase in
tumor oxygenation, which has the potential to make the tumor more susceptible to adjuvant therapies such as radiation
and chemotherapy. Prior studies in breast cancer cells demonstrated that a hypoxic microenvironment diminished NP uptake in vitro; however, mNPHT with intratumoral NP injection in hypoxic tumors increased tumor oxygenation and
delayed tumor growth. In this study, head and neck squamous cell carcinoma (HNSCC) cell lines were incubated in
normoxic, hypoxic, and hyperoxic conditions with iron oxide NP for 4-72 hours. After incubation, the cells were
analyzed for iron uptake by mass spectrometry, Prussian blue staining, and electron microscopy. In contrast to breast
cancer cells, uptake of NPs was increased in hypoxic microenvironments as compared to normoxic conditions in HNSCC cells. In future studies, we will confirm the effect of the oxygen microenvironment on NP uptake and efficacy of mNPHT both in vitro and in vivo.
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