Increased radiosensitivity of colorectal tumors with intra-tumoral injection of low dose of gold nanoparticles

Abstract

The potential of gold nanoparticles (GNPs) as radiosensitizers for the treatment of malignant tumors has been limited by the large quantities of GNPs that must be administered and the requirement for low-energy X-ray irradiation to optimize radiosensitization. In this study, we enhance the radiosensitivity of HCT116 human colorectal cells with tiopronin-coated GNPs (Tio-GNPs) combined with a low-energy X-ray (26 keV effective energy) source, similar to the Papillon 50 clinical irradiator used for topical irradiation of rectal tumors. Sensitizer enhancement ratios of 1.48 and 1.69 were measured in vitro, when the HCT116 cells were incubated with 0.1 mg/mL and 0.25 mg/mL of Tio-GNPs, respectively. In nude mice bearing the HCT116 tumor, intra-tumoral (IT) injection of Tio-GNPs allowed a 94 times higher quantity of Tio-GNPs to accumulate than was possible by intravenous injection and facilitated a significant tumor response. The time following irradiation, for tumors growing to four times their initial tumor volume (4Td) was 54 days for the IT injection of 366.3 μg of Tio-GNPs plus 10 Gy, compared to 37 days with radiation alone (P=0.0018). Conversely, no significant improvement was obtained when GNPs were injected intravenously before tumor irradiation (P=0.6547). In conclusion, IT injection of Tio-GNPs combined with low-energy X-rays can significantly reduce the growth of colorectal tumors.

Keywords:

• gold nanoparticles
• colorectal cancer
• mice
• X-ray
• radiation enhancement

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Increased radiosensitivity of colorectal tumors with intra-tumoral injection of low dose of gold nanoparticles [Corrigendum]

Supplementary material

Figure S1 Tio-GNPs in MEM at concentrations of 0.1 mg/mL (A) and 0.25 mg/mL (B) without FBS were visualized under TEM.

Notes: Magnification of S1A and B: 100,000×.

Abbreviations: FBS, fetal bovine serum; MEM, minimum essential medium; TEM, transmission electron microscopy; Tio-GNPs, tiopronin-coated gold nanoparticles.

Acknowledgments

We would like to thank Doctor AD Bass for helpful suggestions and corrections, François Lessard for providing the original data of the Therapax SXT 150 X-ray beam spectra, Doctor J Constanzo for the technical support in foci counting, and the Electron Microscopy and Histology Research Core of the Faculty of Medicine and Health Science at the Université de Sherbrooke for their electron microscopy services. This work was supported by the Canadian Institutes of Health Research (grant # PPP-122899). Louis Gendron, Brigitte Guérin, Léon Sanche, and Benoit Paquette are members of the Centre de Recherche du CHUS supported by the Fonds de la Recherche du Québec – Santé.

Disclosure

The authors report no conflicts of interest in this work.