(650d) Cancer Microtissues for Rationalized Nanoparticle Based Radiotherapy

Radiotherapy is an integral and highly effective part of cancer therapy applicable in over 50% of the patients affected by cancer. Due to the low specificity of irradiation, the maximal dose is greatly limited in order to not cause damage to healthy tissue. The limited dose oftentimes leads to the survival of a small portion of radio-resistant cells that then grow back causing the cancer to reoccur. Approaches based on high z (atomic number) inorganic nanoparticles have been proposed to locally increase the photoelectric absorption cross-section relative to healthy tissue. However, the complex interplay between the radio-enhancers and the tumor tissue has led to radio-sensitizer drug treatment plans based mostly on empirical decisions. Here, we report on a systematic approach to rationalize radio-enhancer development and combination therapy plans based on quantitative endpoints. We present an advanced in vitro model depicting key features of tumors and report on the nanoparticle uptake and radio-enhancement effects compared to 2D in vitro culture.

L.H.R. Gerken, K. Keevend, Y. Zhang, F.H. L. Starsich, C. Eberhardt, G. Panzarasa, M.T. Matter, A. Wichser, A.s Boss, A. Neels, I.K. Herrmann, Lanthanide-doped Hafnia Nanoparticles for Multimodal Theranostics: Tailoring the Physicochemical Properties and Interactions with Biological Entities, ACS Applied Materials and Interfaces, 2019.