Elucidating the cellular response of silver nanoparticles as a potential combinatorial agent for cisplatin chemotherapy

Renata Rank Miranda*, Micaella Pereira da Fonseca, Barbara Korzeniowska, Lilian Skytte, Kaare Lund Rasmussen, Frank Kjeldsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

BACKGROUND: Combination chemotherapy uses drugs that target different cancer hallmarks, resulting in synergistic or additive toxicity. This strategy enhances therapeutic efficacy as well as minimizes drug resistance and side effects. In this study, we investigated whether silver nanoparticles act as a combinatorial partner to cisplatin. In so doing, we compared post-exposure biological endpoints, intracellular drug accumulation, and changes in the proteome profile of tumoral and normal cell lines.

RESULTS: Combinatorial exposure corresponded to cytotoxicity and oxidative stress in both cell lines, yet was substantially more effective against tumoral cells. Proteome analysis revealed that proteins related to energy metabolism pathways were upregulated in both cell lines, suggesting that combinatorial exposure corresponded to energetic modulation. However, proteins and upstream regulators involved in the cell cycle were downregulated, indicating reduced cell proliferation. The response to oxidative stress was markedly different in both cell lines; downregulation of antioxidant proteins in tumoral cells, yet upregulation of the antioxidant defense system in normal cells. These outcomes may have avoided higher cell death rates in normal cells.

CONCLUSIONS: Taken together, our results indicate that combining silver nanoparticles with cisplatin increases the biological activity of the latter, and the combination warrants further exploration for future therapies.

Original languageEnglish
Article number164
JournalJournal of Nanobiotechnology
Volume18
Number of pages15
DOIs
Publication statusPublished - 10. Nov 2020

Keywords

  • Cell viability
  • Combination chemotherapy
  • Metal uptake
  • Proteomics
  • Silver nanoparticles

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