Hybrid gold nanoparticles coated with organic polymers and antibodies as a platform for cancer theranostics: cytotoxicity assessment and radioactive doping

Since medical radiation is the largest man-made source of radiation
exposure in Western countries, radiation awareness and protection remain
fundamental responsibilities in diagnostic imaging and radiotherapy. It is
well known that ionizing radiation directly and indirectly damages cellular
biomolecules such as DNA, lipids and proteins, which may lead to tissue
dysfunction. Therefore, there is a need to develop optimized strategies to
limit patient radiation doses, while simultaneously improving the
effectiveness of cancer imaging and radiotherapy. Currently, there is a
growing interest to use gold nanoparticles (AuNPs) as radiosensitizers in
medicine, locally enhancing the radiation dose in the tumor tissue by the
production of secondary electrons and free radical species upon external
irradiation. At the University of Namur, AuNPs have been successfully
synthesized and coated with an organic poly-allylamine shell used to
immobilize the monoclonal antibody Cetuximab, targeting the epidermal
growth factor receptor (EGFR). These nanoconjugates were able to
selectively target EGFR-overexpressing cancer cells both in vitro and in
vivo. However, prior to use the Cetuximab-AuNPs in clinical applications,
their cytotoxicity mechanisms in normal, healthy cells should be investigated
properly. For this purpose, we will assess the cell viability, proliferation,
ROS production and DNA damage (repair) in different types of normal cells
upon incubation with Cetuximab-AuNPs. Furthermore, we aim to increase
the theranostic value of the nanoconjugates by optimizing the production
process to load Cetuximab-AuNPs with the theranostic 64Cu radionuclide,
which allows diagnostic PET scanning as well as radiation dose delivery to
the tumor tissue. Finally, we will investigate a potential synergistic
therapeutic effect of the 64Cu dose delivery in cancer cells and the
radiosensitization effect of the gold core upon external irradiation, both in
vitro and in vivo.