Preclinical background

Tumor cell uptake

Nbtxr3 has been demonstrated to be uptaken by mammalian cancer cells. To confirm that the cellular uptake of nanoparticles is mediated through endosomes, transmission electron microscopy (TEM) analysis has been performed.

Performance: cell viability assay

Cell viability was measured after a 24 hour treatment period with, and without ,nbtxr3 , varying irradiation doses (up to 6 Gy). Nbtxr3 used in combination with radiotherapy has shown an increase in efficacy; 1 Gy corresponds to the efficacy of 3 Gy of radiotherapy alone.

Intratumor use

Nbtxr3 has been intratumorously injected to mice bearing a tumor. The time residency of nanoparticles in tumor is at least 15 days, with a good dispersion of the product.

Performance study of nbtxr3 in HCT116 tumor model

Nbtxr3 has been intratumorously injected to mice bearing tumors grafted on the flank. Local irradiation of tumor has been performed. Nbtxr3 leads to a total regression of tumor on all animals compared to 5% glucose-treated mice subjected to radiotherapy alone. After 60 days, 90% of animals are still tumor free when treated with nbtxr3 plus radiotherapy. The group with radiotherapy alone has shown growth of the tumor.

Systemic tolerance of nbtxr3

The tolerance of HCT116 tumor bearing Swiss nude to repeated administrations of nbtxr3 has been explored. This study has permitted the checking of potential acute toxic effects of the product after exaggerated injection compared to the planned one-injection use in humans.