Folic acid receptor-targeted solid lipid nanoparticles to enhance cytotoxicity of letrozole through induction of caspase-3 dependent-apoptosis for breast cancer treatment
Atefeh Yassemi, Soheila Kashanian, Hossein Zhaleh
Abstract
Chemotherapy using cytotoxic agents, such as letrozole (LTZ), is one of the most effective treatments for hormone-dependent breast cancer. Nevertheless, nonspecific targeting of the drug constructs several remarkable systemic toxicities. In this study, we synthesized solid lipid nanoparticles (SLNs) by solvent emulsification evaporation method as LTZ carriers. Nanoparticles were also modified with a cancer cell-targeting ligand, folic acid (FA), and then characterized. Cell membrane damage and cell viability were investigated by lactate dehydrogenase (LDH) and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays, respectively. Caspase-3 activity and TUNEL assays were performed to verify induced apoptosis. Scanning electron microscopy (SEM) exhibited uniform and spherical morphology of the SLNs-LTZ and FA-SLNs-LTZ. The X-ray diffraction (XRD) confirmed LTZ was dispersed as amorphous in the SLNs. The cell culture results revealed that FA-SLNs-LTZ was significantly more cytotoxic than SLNs-LTZ and free drug against MCF-7 cancer cells in vitro, with a 50% inhibitory concentration (IC50) value of 81 ± 0.89 nM, but both nanoformulations had negligible cytotoxicity toward MCF-10A normal cells and they showed promising biocompatibility. Taken together, these findings indicated the evidence of apoptosis as a mechanism of cell death. This study suggests the potential of FA-SLNs-LTZ for inducing apoptosis in a target-specific manner with minimal systemic side effects.