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.

Transient Anions in Radiobiology and Radiotherapy: From Gaseous Biomolecules to Condensed Organic and Biomolecular Solids

“…To treat deep tumors, a radioactive source may have to be encapsulated inside a gold nanoparticle (i.e., in a gold nanocage) [219]. Furthermore, if DNA specificity cannot be achieved in patients, successful treatment may still be possible by intratumor injection of GNPs, as recently shown by Shi et al [220] and Bobyk et al [204].…”

Octaarginine-modified gold nanoparticles enhance the radiosensitivity of human colorectal cancer cell line LS180 to megavoltage radiation

“…Indeed, GNPs have been shown to enhance the sensitivity of HCT116 cells to 26 keV X-rays with a sensitizer enhancement ratio (SER) of 1.69 in vitro. 10 However, megavoltage X-rays are widely used instead of kiloelectronvolt sources in clinical practice. It has been reported that GNPs exhibit efficacy using megavoltage radiation sources in breast, prostate, and lung cancer.…”

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes

“…The enhancement of radiation damage and the biological effects, associated with the individual physical and chemical properties of Pt-CAs and GNPs, have been observed in several in vitro and in vivo studies [23][24][25][26][27][28][29][30][31][32][33][34][35][36]. However, from the results obtained individually with GNPs and Pt-CAs, it became obvious that combining both radiosensitizers in a common carrier could considerably enhance the benefit of chemoradiation therapy (i.e., GNPs produce large quantities of LEEs that would strongly react with any Pt-CAs bound to DNA or other biomolecules vital for cell survival).…”

“…Tumor response was determined in immunodeficient NU/NU nude mice with carboplatin as the CA. According to recent results, the limitation of radiotherapy in colorectal cancer treatment [25] could be improved through the use of a liposomal formulation carrying both a CA and radio enhancer. Preliminary results are concisely presented in this article on this novel method of combining metal nanoparticles with CAs in an effort to enhance the benefits of concomitant chemoradiation therapy.…”