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

Abstract

Minghan Shi,1 Benoit Paquette,1 Thititip Thippayamontri,1 Louis Gendron,2 Brigitte Guérin,1 Léon Sanche1 1Department of Nuclear Medicine and Radiobiology, Center for Research in Radiotherapy, 2Department of Pharmacology-Physiology, University of Sherbrooke, Sherbrooke, QC, CanadaAbstract: 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

Keywords

• Gold nanoparticles
• colorectal cancer
• mice
• x-ray
• radiation enhancement