Lecture Dr. Carine Michiels | The use of nanoparticles as enhancers for radiotherapy: promises and limits

The use of nanoparticles as enhancers for radiotherapy: promises and limits

The use of charged particle radiation therapy in combination with gold nanoparticles (AuNPs) is of particular interest. Our data indicate that the combination of improved internalization through specific targeting and radiosensitization using cetuximab-conjugated AuNPs is a promising strategy for increasing the eradication of cancer cells by protontherapy. Although the radiosensitization effect was initially attributed to a dose-enhancing mechanism, a growing number of studies are challenging this mechanistic hypothesis, highlighting the importance of chemical and biological contributions. Our work demonstrated that thioredoxin reductase revealed is a target for gold nanoparticles, disabling the antioxidant capacities of the cells and thus enhancing their sensitivity to proton irradiation.

Antibody-labeled gold nanoparticles also represent a promising new tool for cancer imaging. In order to translate the in vitro data, the biodistribution of the cetuximab-AuNP nanohybrids was studied in depth. To this end, the biodistribution of ⁸⁹Zr-labeled cetuximab before and after coupling with AuNPs and injected into mice bearing xenografts showed that AuNPs coupled to ⁸⁹Zr-cetuximab led to their specific accumulation in the tumor. 

In parallel, the cytotoxicity of AuNPs conjugated or not to cetuximab in normal human kidney (HK-2), liver (THLE-2) and microvascular endothelial (TIME) cells, the latter being the most sensitive. We also investigated the pharmacokinetics, biodistribution and toxicity after AuNP intravenous administration in healthy mice up to 6 months. These studies deepened the understanding of the risks associated with the use of AuNPs in vivo.

Altogether, our studies demonstrated that targeted radioisotope-labeled gold nanoparticles could be a promising theranostic agent for cancer.