Abstract 857: Metal oxide nanoparticles as adjuvant for radiation therapy

Abstract

Abstract Background: Radiation therapy comprises a fundamental component of modern tumor treatment. Unfortunately, its success is limited by the development of radiation resistances. The emerging field of nanotechnology offers great opportunities for diagnosing, imaging, as well as treating cancer. Metal oxide nanoparticles in particular zinc oxide nanoparticles (ZnO-NP) have been shown to display a selective cytotoxic effect on tumor cells via a yet unknown mechanism. Most likely the generation of reactive oxygen species (ROS), breakdown of mitochondria and DNA damage are involved. The success of radiation therapy equally relies on the generation of ROS, which develop their cytotoxic potential by damaging DNA, proteins and membranes in a fashion that exceeds the repair capacity of tumor cells. Thus, our aim was to evaluate the applicability of ZnO-NP as radiosensitizer to restore the response of tumor cells to radiation therapy. Methods: An AlamarBlueTM assay was used to evaluate the cellular metabolic activity (CMA) of A549 adenocarcinoma cells after treatment with ZnO-NP. To assess cellular viability and cell death a flow cytometric apoptosis assay was applied and genotoxicity of ZnO-NP was analysed by γH2AX foci analysis. The performance of ZnO-NP as radiosensitizer was assessed by a colony formation assay (CFA). Results: We were able to show that ZnO-NP-mediated cytotoxicity is conveyed by dissolved Zn2+ ions as well as by the particles themselves. Treatment with ZnO-NP resulted in double-strand breaks (DSB) of the DNA measured by γH2AX foci analysis. The apoptosis assay could show induction of apoptosis in A549 cells after treatment with 100 µg/ml ZnO-NP for four hours. The colony formation assay showed that irradiation with 2 or 4 Gray, according to dosages that are typically applied in clinical settings, in combination with ZnO-NP treatment could enhance tumor cell death and reduce clonogenic survival. This revealed that ZnO-NP could improve the success of radiation therapy. Conclusions: Our study proves that ZnO-NP exert a cytotoxic and genotoxic effect on human tumor cells. Additionally, we could show, that ZnO-NP are able to serve as radiosensitizer. Combined treatment of human tumor cells with ZnO-NP and irradiation resulted in reduction of tumor cell survival. Since nanoparticles can in principle be targeted selectively to tumor tissue, ZnO-NP could be used to specifically sensitize tumor cells for irradiation while sparing healthy tissue. All in all, the study shows that ZnO-NPs could be a promising antitumor agent. Citation Format: Nadine Wiesmann, Martin Kluenker, Wolfgang Tremel, Juergen Brieger. Metal oxide nanoparticles as adjuvant for radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 857.