Combining ultrasmall gadolinium-based nanoparticles with photon irradiation overcomes radioresistance of head and neck squamous cell carcinoma

Nanomedicine. 2015 Jan;11(1):247-57. doi: 10.1016/j.nano.2014.06.013. Epub 2014 Jun 28.

Abstract

Gadolinium based nanoparticles (GBNs, diameter 2.9±0.2nm), have promising biodistribution properties for theranostic use in-vivo. We aimed at demonstrating the radiosensitizing effect of these GBNs in experimental radioresistant human head and neck squamous cell carcinoma (SQ20B, FaDu and Cal33 cell lines). Combining 0.6mM GBNs with 250kV photon irradiation significantly decreased SQ20B cell survival, associated with an increase in non-reparable DNA double-strand breaks, the shortening of G2/M phase blockage, and the inhibition of cell proliferation, each contributing to the commitment of late apoptosis. Similarly, radiation resistance was overcome for SQ20B stem-like cells, as well as for FaDu and Cal33 cell lines. Using a SQ20B tumor-bearing mouse model, combination of GBNs with 10Gy irradiation significantly delayed tumor growth with an increase in late apoptosis and a decrease in cell proliferation. These results suggest that GBNs could be envisioned as adjuvant to radiotherapy for HNSCC tumors.

Keywords: Gadolinium nanoparticles; Head and neck squamous cell carcinoma (HNSCC); Radioresistance; Radiosensitization; Radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Caspase 2 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • DNA Damage
  • Female
  • Flow Cytometry
  • Gadolinium / chemistry*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Histones / chemistry
  • Humans
  • Mice
  • Mice, Nude
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Nanomedicine
  • Nanoparticles / chemistry*
  • Radiation-Sensitizing Agents / chemistry*
  • Radiotherapy

Substances

  • Histones
  • Radiation-Sensitizing Agents
  • Gadolinium
  • Caspase 2