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

Autor: Lilian Skytte, Kaare Lund Rasmussen, Barbara Korzeniowska, Micaella Pereira Da Fonseca, Renata Rank Miranda, Frank Kjeldsen
Jazyk: angličtina
Předmět:
Zdroj: Journal of Nanobiotechnology
Journal of Nanobiotechnology, Vol 18, Iss 1, Pp 1-15 (2020)
Rank Miranda, R, Pereira da Fonseca, M, Korzeniowska, B, Skytte, L, Lund Rasmussen, K & Kjeldsen, F 2020, ' Elucidating the cellular response of silver nanoparticles as a potential combinatorial agent for cisplatin chemotherapy ', Journal of Nanobiotechnology, vol. 18, 164 . https://doi.org/10.1186/s12951-020-00719-x
ISSN: 1477-3155
DOI: 10.1186/s12951-020-00719-x
Popis: 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.
Databáze: OpenAIRE
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