Summary

Today, more than half of all cancer patients receive radiotherapy as part of their treatment. However, radiotherapy efficacy is often limited by healthy tissues toxicity and needs to be optimized. One relevant solution is to increase the radiation dose deposition from within the tumor cells. The presence of high atomic number (high-Z) elements within the X-ray pathway increases the probability of interaction with ionizing radiation as compared with tissues (composed of low-Z elements). Likewise, mammalian cells can handle materials at the nanoscale. Therefore, materials made of high-Z elements designed at the nanoscale can enhance the deposit of the radiation dose at the cancer cell level.

Still, the most relevant design of these nano-objects has been scarcely explored. Here, we hypothesize that the packing of high-Z elements within the nano-object is a key parameter when considering its design. We used gold and probe how its packing at the nanoscale can achieve the best probability of interaction with ionizing radiation. […]

Summary

Aim: There is considerable interest in approaches that could improve the therapeutic window of radiotherapy. In this study, hafnium oxide nanoparticles were designed that concentrate in tumor cells to achieve intracellular highenergy dose deposit. Materials & methods: Conventional methods were used, implemented in different ways, to explore interactions of these high-atomicnumber nanoparticles and ionizing radiation with biological systems.

Results: Using the Monte Carlo simulation, these nanoparticles, when exposed to highenergy photons, were shown to demonstrate an approximately ninefold radiation dose enhancement compared with water. Importantly, the nanoparticles show satisfactory dispersion and persistence within the tumor and they form clusters in the cytoplasm of cancer cells. Marked antitumor activity is demonstrated in human cancer models. Safety is similar in treated and control animals as demonstrated by a broad program of toxicology evaluation.

Conclusion: These findings, supported by good tolerance, provide the basis for developing this new type of nanoparticle as a promising anticancer approach in human patients.