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

Gadolinium based nanoparticles (GBNs, diameter 2.9 ± 0.2 nm), 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 0.6 mM GBNs with 250 kV 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 10 Gy 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.From the Clinical EditorGadolinium-based nanoparticles are studied as radiosensitizing theranostic agents to address head and neck squamous cell carcinoma in this novel study, demonstrating a promising adjuvant to radiotherapy for these often treatment resistant tumors.

Graphical AbstractGadolinium based nanoparticles (GBNs), less than 5 nm in diameter, combined with radiotherapy increase irreversible DNA double-strand breaks and mitotic catastrophe, leading to late apoptosis and therefore cell death. This radiosensitizing effect of GBNs is demonstrated in vitro in three radioresistant human head and neck squamous cell carcinoma (HNSCC) cell lines, and in vivo in mice bearing human SQ20B HNSCC tumor.Figure optionsDownload high-quality image (88 K)Download as PowerPoint slide