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

Journal of Nanobiotechnology

Micaella Pereira da Fonseca¹  Renata Rank Miranda¹  Barbara Korzeniowska¹  Frank Kjeldsen¹  Kaare Lund Rasmussen²  Lilian Skytte² 

[1] Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense, Denmark;Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230, Odense, Denmark;

关键词: Silver nanoparticles;    Combination chemotherapy;    Proteomics;    Cell viability;    Metal uptake;   

DOI  :  10.1186/s12951-020-00719-x

来源: Springer

【 摘 要 】

BackgroundCombination 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.ResultsCombinatorial 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.ConclusionsTaken 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.

【 授权许可】

CC BY