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Elucidating the cellular response of silver nanoparticles as a potential combinatorial agent for cisplatin
Renata Rank Miranda1, Micaella Pereira da Fonseca2, Barbara Korzeniowska2
1Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, 5230, Denmark. renatam.bio@gmail.com.
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.
Insights
Combining silver nanoparticles with cisplatin enhances chemotherapy efficacy against cancer cells. This combination therapy shows promise by increasing drug activity and reducing tumor cell proliferation while protecting normal cells.
Area of Science:
- Nanomedicine
- Cancer Biology
- Chemotherapy
Background:
- Combination chemotherapy leverages drugs targeting diverse cancer hallmarks for enhanced efficacy and reduced resistance.
- Investigated silver nanoparticles (AgNPs) as a potential combinatorial partner with cisplatin chemotherapy.
Purpose of the Study:
- To evaluate the synergistic effects of combining silver nanoparticles with cisplatin.
- To compare cellular responses, drug accumulation, and proteome changes in tumoral and normal cell lines.
Main Methods:
- Utilized combination chemotherapy with silver nanoparticles and cisplatin.
- Performed proteome analysis to assess cellular pathway modulation.
- Compared cytotoxicity and oxidative stress markers in different cell lines.
Main Results:
- Combined treatment exhibited greater cytotoxicity against tumoral cells compared to normal cells.
- Proteome analysis revealed altered energy metabolism and downregulated cell cycle proteins in both cell types.
- Tumoral cells showed decreased antioxidant proteins, while normal cells upregulated antioxidant defenses, potentially reducing normal cell toxicity.
Conclusions:
- Combining silver nanoparticles with cisplatin potentiates the biological activity of cisplatin.
- The synergistic effects suggest this combination warrants further investigation for novel cancer therapies.
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