title: Oxygen microenvironment affects the uptake of nanoparticles in head and neck tumor cells.
abstract: 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 uptakein 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 bothin vitroandin vivo.
authors.affiliation: Department of Surgery, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH USA 03756 ; Geisel School of Medicine, 1 Rope Ferry Road, Hanover, NH USA 03755.
authors.forename: Eunice Y
authors.initials: EY
authors.lastname: Chen
authors.affiliation: Department of Surgery, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH USA 03756.
authors.forename: Sassan
authors.initials: S
authors.lastname: Hodge
authors.affiliation: Department of Surgery, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH USA 03756.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tai
authors.affiliation: Department of Radiology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH USA 03756.
authors.forename: Huagang
authors.initials: H
authors.lastname: Hou
authors.affiliation: Department of Radiology, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH USA 03756.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Khan
authors.affiliation: Department of Surgery, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH USA 03756 ; Geisel School of Medicine, 1 Rope Ferry Road, Hanover, NH USA 03755 ; Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
authors.affiliation: Department of Surgery, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH USA 03756 ; Geisel School of Medicine, 1 Rope Ferry Road, Hanover, NH USA 03755 ; Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: Kimberley S
authors.initials: KS
authors.lastname: Samkoe
keywords: head and neck cancer; hypoxia; magnetic nanoparticle hyperthermia