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Cellular toxicology and mechanism of the response to silver-based nanoparticle exposure in Ewing's sarcoma cells
Veronica da Silva Ferreira1,2, Mateus Ferreira Conz Eugenio1,2, Elaine Del Nery Dos Santos3
1Laboratory of Microscopy Applied to Life Science-Lamav, National Institute of Metrology, Quality and Technology-Inmetro, Duque de Caxias, RJ, 25250-020, Brazil.
Abstract:
Ewing's sarcoma is the most aggressive connective tissue tumor, mainly affecting children and adolescents; the 5 year survival rate is only 50%. Current treatments have poor effectiveness, and more efficient treatments are being sought. Silver-based nanoparticles, such as silver chloride nanoparticles (AgCl-NPs) and silver/silver chloride (Ag/AgCl-NPs) nanoparticles, can be biologically produced and can release Ag+ ions into solution; however, their antitumor activity has been minimally investigated. The aim of this study was to evaluate the antitumor potential of AgCl-NPs and Ag/AgCl-NPs against Ewing's sarcoma cells. A673 cells (Ewing's sarcoma) were treated for 72 h with 0-12.5 μg ml-1 of Ag/AgCl-NPs or 0-40 μg ml-1 of AgCl-NPs. Human cells from the RPE-1 cell line (pigmented retinal epithelium) were used as a model of nontumor cells. The RPE-1 cells were less affected by the administration of AgCl-NPs or Ag/AgCl-NPs, with small reductions in the number of cells and viability and a small increase in apoptosis rates, while lysosomal damage, changes in reactive oxygen species (ROS) production, loss of mitochondrial membrane potential and alterations in microfilaments or cell areas were not observed. A673 tumor cells had significantly reduced number and viability levels when treated with AgCl-NPs, with reductions of 65.05% and 99.17%, respectively, whereas with Ag/AgCl-NP treatment, reductions of 65.53% and 92.51% were observed, respectively. When treated with silver-based nanoparticles, A673 cells also showed a significant increase in ROS production and loss of mitochondrial membrane potential, which culminated in an increase in the percentage of apoptosis among the population. Lysosomal damage was also observed when A673 cells were treated with the highest concentration of AgCl-NPs. In conclusion, the results showed that both AgCl-NPs and Ag/AgCl-NPs had some antitumor activity with minimal effects against healthy cells, which demonstrated the possibility of their use in cancer therapy.
Insights
Silver nanoparticles show promise in treating aggressive Ewing's sarcoma. Silver chloride nanoparticles (AgCl-NPs) and silver/silver chloride nanoparticles (Ag/AgCl-NPs) effectively reduced tumor cell viability and increased apoptosis, with minimal impact on healthy cells.
Area of Science:
- Nanotechnology
- Biomedical Engineering
- Oncology
Background:
- Ewing's sarcoma is an aggressive pediatric cancer with a low survival rate.
- Current treatments for Ewing's sarcoma are often ineffective, necessitating novel therapeutic approaches.
- Silver-based nanoparticles (AgCl-NPs, Ag/AgCl-NPs) have shown potential but their antitumor activity requires further investigation.
Purpose of the Study:
- To evaluate the antitumor potential of silver chloride nanoparticles (AgCl-NPs) and silver/silver chloride nanoparticles (Ag/AgCl-NPs) against Ewing's sarcoma cells.
- To assess the safety and efficacy of these nanoparticles on both cancerous and non-cancerous cell lines.
Main Methods:
- Ewing's sarcoma (A673) and non-tumorigenic retinal pigment epithelium (RPE-1) cells were treated with varying concentrations of AgCl-NPs and Ag/AgCl-NPs for 72 hours.
- Cell viability, proliferation, apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential, and lysosomal damage were assessed.
Main Results:
- AgCl-NPs and Ag/AgCl-NPs significantly reduced A673 cell viability and number, inducing apoptosis.
- Treatment with these nanoparticles increased ROS production and decreased mitochondrial membrane potential in tumor cells.
- Non-tumorigenic RPE-1 cells exhibited minimal adverse effects, showing only slight reductions in cell number and viability.
Conclusions:
- Silver chloride nanoparticles and silver/silver chloride nanoparticles demonstrate significant antitumor activity against Ewing's sarcoma cells.
- These nanoparticles exhibit a favorable safety profile, with minimal toxicity to healthy cells.
- The findings suggest that AgCl-NPs and Ag/AgCl-NPs hold potential for development as novel cancer therapeutics for Ewing's sarcoma.
