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The Radiosensitizing Effect of Zinc Oxide Nanoparticles in Sub-Cytotoxic Dosing is Associated with Oxidative Stress In Vitro

: Meyer, Till Jasper; Scherzad, Agmal; Moratin, Helena; Gehrke, Thomas; Killisperger, Julian; Hagen, Rudolf; Wohlleben, Gisela; Polat, Bülent; Dembski, Sofia; Kleinsasser, Norbert Helmut; Hackenberg, Stephan

Fulltext ()

Materials 12 (2019), No.24, Art. 4062, 12 pp.
ISSN: 1996-1944
Journal Article, Electronic Publication
Fraunhofer ISC ()
zinc oxide nanoparticles; Oxidative DNA damage; irradiation; head and neck squamous cell carcinoma; cell culture

Radioresistance is an important cause of head and neck cancer therapy failure. Zinc oxide nanoparticles (ZnO-NP) mediate tumor-selective toxic effects. The aim of this study was to evaluate the potential for radiosensitization of ZnO-NP. The dose-dependent cytotoxicity of ZnO-NP20 nm and ZnO-NP100 nm was investigated in FaDu and primary fibroblasts (FB) by an MTT assay. The clonogenic survival assay was used to evaluate the effects of ZnO-NP alone and in combination with irradiation on FB and FaDu. A formamidopyrimidine-DNA glycosylase (FPG)-modified single-cell microgel electrophoresis (comet) assay was applied to detect oxidative DNA damage in FB as a function of ZnO-NP and irradiation exposure. A significantly increased cytotoxicity after FaDu exposure to ZnO-NP20 nm or ZnO-NP100 nm was observed in a concentration of 10 μg/mL or 1 μg/mL respectively in 30 μg/mL of ZnO-NP20 nm or 20 μg/mL of ZnO-NP100 nm in FB. The addition of 1, 5, or 10 μg/mL ZnO-NP20 nm or ZnO-NP100 nm significantly reduced the clonogenic survival of FaDu after irradiation. The sub-cytotoxic dosage of ZnO-NP100 nm increased the oxidative DNA damage compared to the irradiated control. This effect was not significant for ZnO-NP20 nm. ZnO-NP showed radiosensitizing properties in the sub-cytotoxic dosage. At least for the ZnO-NP100 nm, an increased level of oxidative stress is a possible mechanism of the radiosensitizing effect.