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Open AccessArticle

Synergistic Radiosensitization by Gold Nanoparticles and the Histone Deacetylase Inhibitor SAHA in 2D and 3D Cancer Cell Cultures

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Department of Biochemistry and Molecular Biology, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary
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Doctoral School of Biology, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary
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Institute of Biochemistry, Biological Research Centre, Szeged, Temesvári krt. 62, H-6726 Szeged, Hungary
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Department of Oncotherapy, University of Szeged, Korányi fasor 12, H-6720 Szeged, Hungary
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Department of Applied and Environmental Chemistry, University of Szeged, Rerrich Béla tér 1, H-6720 Szeged, Hungary
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Department of Pathology, University of Szeged, Állomás utca 2, H-6720 Szeged, Hungary
*
Author to whom correspondence should be addressed.
Nanomaterials 2020, 10(1), 158; https://doi.org/10.3390/nano10010158 (registering DOI)
Received: 17 December 2019 / Revised: 4 January 2020 / Accepted: 13 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue Application of Nanoscale Materials for Cancer Diagnostic and Therapy)
Radiosensitizing agents are capable of augmenting the damage of ionizing radiation preferentially on cancer cells, thereby increasing the potency and the specificity of radiotherapy. Metal-based nanoparticles have recently gathered ground in radio-enhancement applications, owing to their exceptional competence in amplifying the cell-killing effects of irradiation. Our aim was to examine the radiosensitizing performance of gold nanoparticles (AuNPs) and the chromatin-modifying histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alone and in combination. We observed that the colony-forming capability of cancer cells decreased significantly and the DNA damage, detected by γH2AX immunostaining, was substantially greater after combinational treatments than upon individual drug exposures followed by irradiation. Synergistic radiosensitizing effects of AuNPs and SAHA were proven on various cell lines, including radioresistant A549 and DU-145 cancer cells. 3D cultures often manifest radio- and drug-resistance, nevertheless, AuNPs in combination with SAHA could effectively enhance the potency of irradiation as the number of viable cells decreased significantly when spheroids received AuNP + SAHA prior to radiotherapy. Our results imply that a relaxed chromatin structure induced by SAHA renders the DNA of cancerous cells more susceptible to the damaging effects of irradiation-triggered, AuNP-released reactive electrons. This feature of AuNPs should be exploited in multimodal treatment approaches. View Full-Text
Keywords: radiosensitization; gold nanoparticles; histone deacetylase inhibitor; combinational treatment; DNA damage; 3D cell culture radiosensitization; gold nanoparticles; histone deacetylase inhibitor; combinational treatment; DNA damage; 3D cell culture
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Igaz, N.; Szőke, K.; Kovács, D.; Buhala, A.; Varga, Z.; Bélteky, P.; Rázga, Z.; Tiszlavicz, L.; Vizler, C.; Hideghéty, K.; Kónya, Z.; Kiricsi, M. Synergistic Radiosensitization by Gold Nanoparticles and the Histone Deacetylase Inhibitor SAHA in 2D and 3D Cancer Cell Cultures. Nanomaterials 2020, 10, 158.

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