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Journal of Nanomaterials
Volume 2015 (2015), Article ID 840594, 11 pages
http://dx.doi.org/10.1155/2015/840594
Research Article

Radiosensitizing and Hyperthermic Properties of Hyaluronan Conjugated, Dextran-Coated Ferric Oxide Nanoparticles: Implications for Cancer Stem Cell Therapy

1Department of Radiation Oncology, Beaumont Health System, Royal Oak, MI 48073, USA
2Department of Physics, Oakland University, Rochester, MI 48309, USA
3Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA

Received 19 August 2015; Accepted 19 November 2015

Academic Editor: Piaoping Yang

Copyright © 2015 Ranjeeta Thapa et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Cytotoxicity, radiosensitivity, and hyperthermia sensitivity of hyaluronan-mediated dextran-coated super paramagnetic iron oxide nanoparticles (HA-DESPIONs) were assessed in CD44-expressing head and neck squamous cell carcinoma (HNSCC) cell lines at clinically relevant radiation dose and temperatures. Low-passage HNSCC cells were exposed to HA-DESPIONs and cytotoxicity was assessed using MTT assay. Radiosensitizing properties of graded doses of HA-DESPIONs were assessed in both unsorted and CD44-sorted cells using clonogenic assay in combination with 2 Gy exposure to X-rays. Hyperthermia-induced toxicity was measured at 40°C, 41°C, and 42°C using clonogenic assay. Cell death was assessed 24 hours after treatment using a flow cytometry-based apoptosis analysis. Results showed that HA-DESPIONs were nontoxic at moderate concentrations and did not directly radiosensitize the cell lines. Further, there was no significant difference in the radiosensitivity of and cells. However, HA-DESPIONs enhanced the effect of hyperthermia which resulted in reduced cell survival that appeared to be mediated through apoptosis. We demonstrated that HA-DESPIONs are nontoxic and although they do not enhance radiation sensitivity, they did increase the effect of local hyperthermia. These results support further development of drug-attached HA-DESPIONs in combination with radiation for targeting cancer stem cells (CSCs) and the development of an alternating magnetic field approach to activate the HA-DESPIONs attached to CSCs.