Radiosensitization of resistant (Head and Neck) tumor cells by metal nanoparticles

Abstract : Selective targeting of radiation effects to tumors represents a challenge in radiotherapy. Metal nanoparticles (gadolinium, gold, platinum) are preferentially internalized bytumor cells and have been recognized to locally amplify the radiation dose upon irradiation. Nanoparticles delivered in tumor cells might increase tumor­specificity andefficiency of radiotherapy. The physical mechanisms related to the radiation dose amplification by nanoparticles have been already well described; however, cellularstructures targeted by nanoparticles remain unknown. The DNA molecule is the most sensitive and critical cell structure in the cell concerning the effects of ionizingradiation. A question remains open of whether a damage to the nucleus is necessary for the radiosensitization exerted by gadolinium and other nanoparticles.We studied the effect of 3 nm gadolinium based nanoparticles (GdBNs) on the induction and repair of DNA double­strand breaks (DSBs) in the nuclear DNA of U87tumor cells irradiated with g­rays. We used sensitive method of DSB detection based on confocal fluorescence microscopy coupled with immunodetection of twoindependent DSB markers, gH2AX and 53BP1. Our experiments brought surprising results. In the conditions where GdBNs amplify the radiation effects, they remain localized in the cytoplasm and their influence onDSB induction and repair is only insignificant. This suggests that the radiosensitization mediated by GdBNs and potentially other nanoparticles is a cytoplasmic event thatis independent of the nuclear DNA breakage (a phenomenon commonly accepted as the explanation of biological radiation effects). Based on recognized intracellularlocalization of nanoparticles studied, we hypothesize about possible non­DNA targets for (some) nanoparticles.