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

الملخص EN

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 C D 44 h i g h and C D 44 l o w 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.