Synergistic radiosensitization by gold nanoparticles and the histone deacetylase inhibitor SAHA in 2D and 3D cancer cell cultures

Nóra Igaz, Krisztina Szőke, Dávid Kovács, Andrea Buhala, Zoltán Varga, Péter Bélteky, Zsolt Rázga, László Tiszlavicz, Csaba Vizler, Katalin Hideghéty, Zoltán Kónya, Mónika Kiricsi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number158
JournalNanomaterials
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 2020

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Keywords

  • 3D cell culture
  • Combinational treatment
  • DNA damage
  • Gold nanoparticles
  • Histone deacetylase inhibitor
  • Radiosensitization

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)

Cite this

Igaz, N., Szőke, K., Kovács, D., Buhala, A., Varga, Z., Bélteky, P., Rázga, Z., Tiszlavicz, L., Vizler, C., Hideghéty, K., Kónya, Z., & Kiricsi, M. (2020). Synergistic radiosensitization by gold nanoparticles and the histone deacetylase inhibitor SAHA in 2D and 3D cancer cell cultures. Nanomaterials, 10(1), [158]. https://doi.org/10.3390/nano10010158