Antitumoral and Immunogenic Capacity of β-D-Glucose-Reduced Silver Nanoparticles in Breast Cancer

Immunogenic cell death (ICD) is a type of cell death capable of stimulating immunity against cancer through danger signals that lead to an adaptive immune response. Silver nanoparticles (AgNPs) have been shown to have a cytotoxic effect on cancer cells; however, their mechanism of action is not fully understood. The present study synthesized, characterized, and evaluated the cytotoxic effect of beta-D-glucose-reduced AgNPs (AgNPs-G) against breast cancer (BC) cells in vitro; and assess the immunogenicity of cell death in vitro and in vivo. The results showed that AgNPs-G induce cell death in a dose-dependent manner on BC cell lines. In addition, AgNPs show antiproliferative effects by interfering with the cell cycle. Regarding the detection of damage-associated molecular patterns (DAMPs), it was found that treatment with AgNPs-G induces calreticulin exposure and the release of HSP70, HSP90, HMGB1, and ATP. In vivo, prophylactic vaccination did not prevent tumor establishment; however, tumor weight was significantly lower in AgNPs-G vaccinated mice, while the survival rate increased. In conclusion, we have developed a new method for the synthesis of AgNPs-G, with in vitro antitumor cytotoxic activity on BC cells, accompanied by the release of DAMPs. In vivo, immunization with AgNPs-G failed to induce a complete immune response in mice. Consequently, additional studies are needed to elucidate the mechanism of cell death that leads to the design of strategies and combinations with clinical efficacy.

Automated summary

This study synthesized and characterized beta-D-glucose-reduced silver nanoparticles (AgNPs-G), and evaluated their cytotoxic effect on breast cancer cells in vitro. The study also investigated the immunogenicity of cell death induced by AgNPs-G in vitro and in vivo. The results showed that AgNPs-G can induce dose-dependent cell death and inhibit proliferation of breast cancer cells. Treatment with AgNPs-G also led to exposure of calreticulin and release of HSP70, HSP90, HMGB1, and ATP. In vivo, immunization with AgNPs-G did not completely induce immune response, but it reduced tumor weight and improved survival rate.