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

• Published in: International journal of nanomedicine 2016-01, Vol.11, p.5323-5333
• Main Authors: Shi, Minghan, Paquette, Benoit, Thippayamontri, Thititip, Gendron, Louis, Guérin, Brigitte, Sanche, Léon
• Format: Article
• Language: English
• Subjects: Animals; Brain cancer; Cadmium telluride; Cancer therapies; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - radiotherapy; DNA Breaks, Double-Stranded - drug effects; DNA Breaks, Double-Stranded - radiation effects; Dosimetry; Energy; Gastrointestinal diseases; Geometry; Gold - chemistry; Gold nanoparticles; HCT116 Cells - drug effects; HCT116 Cells - radiation effects; Humans; Injections, Intralesional; Ionizing radiation; Ligands; Male; Metal Nanoparticles - administration & dosage; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; mice; Mice, Nude; Nanoparticles; Original Research; radiation enhancement; Radiation therapy; Radiation-Sensitizing Agents - administration & dosage; Radiation-Sensitizing Agents - chemistry; Sensors; Studies; Tiopronin - chemistry; Tumors; x-ray; X-Rays; Xenograft Model Antitumor Assays
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S97541

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 ( =0.0018). Conversely, no significant improvement was obtained when GNPs were injected intravenously before tumor irradiation ( =0.6547). In conclusion, IT injection of Tio-GNPs combined with low-energy X-rays can significantly reduce the growth of colorectal tumors.