In current scenario, silver nanoparticles (Ag NPs) have been widely used in clinical and household products due to their broad spectrum antibacterial activity. But the cytotoxicity and genotoxicity associated with Ag NPs at higher concentration hindered its 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 overcoming various drawbacks associated with non specific targeting. The albumin coating enhanced the stability of Ag NPs and also provide 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 depict admirable binding, especially in case of MCF-7 (FR-positive cells) having abundant folate receptor (FR) on its surface that leads to their enhanced cellular internalization as compared to A549 cells (FR negative cells). The cell viability assay corroborates a better therapeutic efficacy of prepared NPs against MCF-7 cells as compared to A549 cells. The flow cytometer analysis reveals reactive oxygen species (ROS) increment that leads to oxidative stress induced apoptosis in both the cells. 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 NPs concentration. In future, these targeted albumin stabilized Ag NPs could provide a more safe and effective alternative approach in the field of cancer therapy.
IntroductionIn recent years, metal and semiconductor nanoparticles found tremendous applications in the field of nanomedicine [1-3]. The triumph of food and drug administration (FDA) approved Acticoat (Ag NPs based wound dressing bandage) develop tremendous interest among the scientific community [4]. Since then silver nanoparticles have been extensively studied either alone or in composites form for their antibacterial and anticancer potential [5-8]. Moreover, our previous studies corroborates that apart from disturbing the membrane integrity and normal function of the cells, Ag NPs by themselves or in combination with other therapeutic agents successfully induce apoptosis in various human cancer cells [2]. The therapeutic potential of Ag NPs lies in their ability to augment the ROS generation and activate mitochondria dependent apoptosis [9]. However, major drawbacks associated with Ag NPs such as genotoxicity and DNA damaging capability hindered their therapeutic applications [10-11]. This provokes a need to develop a safe and effective system for efficient delivery of Ag NPs with enhanced therapeutic efficacy at lowest possible Ag NPs concentrations and thereby provide an alternative mode of cancer therapy.In this regard, protein based nanoparticles have been emerged as a potential candidate for therapeutic applications because of the...