Palladium Nanocubes (Pd NCs) and Thiol-PEG Modified Pd NCs (Pd NCs-PEG) for Combating LN229 and U118 Glioblastoma Cells

The rising cancer incidence highlights the need for the ongoing advancement of more efficient therapeutic approaches. Glioblastoma multiforme is one of the cancers with the worst prognosis; hence, in these studies, we developed nanoradiosensitizers that improve the efficiency of irradiation of glioblastoma cells with a high-energy proton beam. For this purpose, ∼12 nm cubic palladium nanoparticles (Pd NCs) were synthesized as an alternative to the more commonly used and more expensive gold nanoparticles (Au NPs). Moreover, Pd NCs were additionally biofunctionalized covalently with thiolated poly(ethylene glycol) (PEG-SH) to reduce their cytotoxicity. Then, in vitro studies were performed on selected glioblastoma (LN229 and U118) cell lines. At equivalent concentrations, Pd NCs-PEG outperformed the unmodified Pd NCs in terms of cytocompatibility while not significantly affecting cellular uptake in either of the tested cell lines. In the context of radiosensitization studies, a statistically significant difference in the radiosensitizing effect of both types of nanoparticles toward U118 cells was observed in favor of Pd NCs-PEG. This correlates with the holotomographic microscopy experiment, which showed that U118 cells showed increased Pd NCs/Pd NCs-PEG uptake compared to LN229 cells. Finally, Fourier-transform infrared spectroscopy (FTIR) revealed chemical changes in glioblastoma cells – mainly in the composition of proteins and sugars – induced by NPs and/or the proton beam. In conclusion, Pd NCs show promising radiosensitizing properties, and their modification with PEG-SH allows obtaining more cytocompatible sensitizers to improve the efficiency of cell irradiation with a proton beam.