Tumor-targeted folate-decorated albumin-stabilised silver nanoparticles induce apoptosis at low concentration in human breast cancer cells

Abstract

At the present time, silver nanoparticles (Ag NPs) have been widely used in clinical and household products due to their broad spectrum antibacterial activity. However, the cytotoxicity and genotoxicity associated with Ag NPs at higher concentration hinders their applications in the field of cancer therapy. The current study exploits the folate-mediated delivery of bovine serum albumin (BSA) stabilized Ag NPs and thereby overcomes various drawbacks associated with non-specific targeting. The albumin coating enhanced the stability of the Ag NPs and also provided a surface for folate conjugation via carbodiimide reaction. Physicochemical characterization confirms the formation of folate-decorated albumin-stabilized Ag NPs (FA-BSA-Ag NPs). The prepared nanoparticles show remarkable binding, especially in the case of MCF-7 (FR-positive) cells having abundant folate receptors (FR) on their surface that leads to enhanced cellular internalization as compared to A549 (FR negative) cells. The cell viability assay corroborates the better therapeutic efficacy of the prepared NPs against MCF-7 cells as compared to A549 cells. Flow cytometer analysis reveals an increase in reactive oxygen species (ROS) that leads to oxidative stress-induced apoptosis in both the cell lines. Further cell cycle, morphological and nuclear analysis suggests characteristic apoptosis indications, which was further confirmed by gene expression analysis. Altogether, these studies implied that the tumor-targeted FA-BSA-Ag NPs induce apoptosis in MCF-7 cells at much lower Ag NP concentration. In future, these targeted albumin stabilized Ag NPs could provide a more safe and effective alternative approach in the field of cancer therapy.