Synthesis and Characterization of Folic Acid Conjugated Gemcitabine Tethered Silver Nanoparticles (FA-GEM-AgNPs) for Targeted Delivery

Abstract

Background: Silver nanoparticles (AgNPs) have attracted considerable interest in the medical industry due to their physicochemical properties, small size, and surface plasmon behavior. Their smaller particle size and instability in blood circulation leads to toxicity due to its aggregation as Ag+ ions and accumulation at the deepseated organ. In the present study, we aimed at reducing the toxicity of AgNPs by conjugation with an anticancer drug GEM and to improve their internalization through folate receptors-mediated endocytosis by capping the nanoparticles with folic acid (FA).

Methods: One-pot facile synthesis of FA capped silver nanoparticles (FA-AgNPs) has been achieved by using FA as a reducing agent. FA-AgNPs were mixed with Gemcitabine (GEM) to obtain tethered FA-GEM-AgNPs. Nanoparticles were characterized by Dynamic Light Scattering (DLS), UV-Visible spectroscopy, Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Analysis (EDAX), Selected Area Electron Diffraction (SAED), and Atomic Absorption Spectroscopy (AAS). The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cytotoxic effect of the prepared nanoformulations. The apoptotic cell death induced by FA-GEM-AgNPs in breast cancer cells were monitored with Acridine orange (AO)/Ethidium Bromide (EtBr) staining.

Conclusion: Compared to GEM and AgNPs, FA-GEM-AgNPs showed enhanced cytotoxic effect and internalization in MDA-MB-453 breast cancer cell line. FA-GEM-AgNPs could be an ideal candidate for targeting cancer cells via folate receptor-mediated endocytosis.

Keywords: Breast cancer; MDA-MB-453; chemical reduction; folate receptor; folic acid reduction; gemcitabine; metallic nanoparticles; silver nanoparticles.