(65d) Design and Development of Inorganic Nanoparticles for Radioenhancement Therapy

Nanoparticle-based radio-enhancement has the prospect to improve cancer cell eradication by amplifying the damage caused by (X-ray) irradiation through ejection of secondary particles (electrons) leading to further oxidative stress. Gold nanoparticles are a natural choice because of their high atomic number and biological compatibility and are therefore the most researched nanoparticles. However, due to the heterogeneous results and the lack in mechanistic understanding, such nanoparticle systems have not yet entered clinics¹. Most recently, nanoparticles based on more exotic hafnium dioxide have shown promising results in first clinical studies². There is increasing evidence that radio-enhancement efficacy does not solely depend on high atomic numbers³ but involves a complex cascade of secondary reactions.

Here, we will present a comprehensive nanoparticle-based radio-enhancement study including a selection of inorganic oxide nanoparticles (TiO₂, ZrO₂, HfO₂) with comparable morphologies, sizes and surface chemistries. We will report on uptake, subcellular distribution and radio-enhancement effects in radio-sensitive and resistant cells using clinically relevant exposure settings. The radio-enhancement efficacies are then benchmarked against the gold standards in the same exposure setting. We also show how the nanoparticles can be tailored to incorporate multimodal imaging possibilities⁴. Our comprehensive analysis will pave the way for a more rationalized nanoparticle design and development for nanoparticle-based radio-enhancement studies.

References

1. Ricketts, K.; Ahmad, R.; Beaton, L.; Cousins, B.; Critchley, K.; Davies, M.; Evans, S.; Fenuyi, I.; Gavriilidis, A.; Harmer, Q. J.; et al. Recommendations for Clinical Translation of Nanoparticle-Enhanced Radiotherapy. The British Journal of Radiology 2018, 91 (1092), 20180325.
2. Bonvalot, S.; Pechoux, C. L.; Baere, T. D.; Kantor, G.; Buy, X.; Stoeckle, E.; Terrier, P.; Sargos, P.; Coindre, J. M.; Lassau, N.; et al. First-in-Human Study Testing a New Radioenhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas. Clin Cancer Res 2017, 23 (4), 908–917.
3. Cui, L.; Her, S.; Borst, G. R.; Bristow, R. G.; Jaffray, D. A.; Allen, C. Radiosensitization by Gold Nanoparticles: Will They Ever Make It to the Clinic? Radiotherapy and Oncology 2017, 124 (3), 344–356.
4. Gerken, L. R. H.; Keevend, K.; Zhang, Y.; Starsich, F. H. L.; Eberhardt, C.; Panzarasa, G.; Matter, M. T.; Wichser, A.; Boss, A.; Neels, A.; et al. Lanthanide-Doped Hafnia Nanoparticles for Multimodal Theranostics: Tailoring the Physicochemical Properties and Interactions with Biological Entities. ACS Appl. Mater. Interfaces 2019, 11 (1), 437–448.