Unveiling the Biotoxicity Mechanisms of Cancer-Selective Thulium Oxide Nanoparticles

High-Z nanoparticles (NPs) have the potential to revolutionize cancer radiotherapy by radiosensitising tumours. This is particularly important for radioresistant cancers such as glioblastoma. A newer NP candidate in this area is thulium oxide nanoparticles (TmNPs). However, prior to clinical assessment, ideal NP characteristics, including biocompatibility, biosafety, and preferential uptake in cancer, should be assessed. This in vitro study compares the effects of TmNP treatment, without radiation, on 9L gliosarcoma (9LGS), a well-established glioblastoma cell model, with exposure to Madin Darby Canine Kidney (MDCK) cells, a widely used non-cancerous cell model. The findings demonstrated selective uptake of TmNPs in 9LGS over MDCK following treatment. A biological assessment of toxicity confirmed minimal long-term effects on MDCK, whilst TmNPs were observed to induce some notable cell death in 9LGS. Excessive TmNP uptake in 9LGS over time was observed to induce cell vacuolisation, which resulted in cell death via necrosis. It was concluded that this was the explanation for the underlying mechanisms of TmNP toxicity in cancer cells. This study was therefore able to demonstrate not only that TmNPs are a biocompatible, cancer-selective candidate for radiosensitiser usage, but further provided a theory to explain its mechanisms of cancer cell toxicity.