Preparation and investigation the anti-tumoral effects of juglone-loaded human serum albumin (HSA) nanoparticles targeting LHRH receptor on T47D and SKOV3 cell lines

Abstract

Introduction: As a natural phytochemical compound, juglone present in different parts of walnut and shows antitumuoral activity. Aim: In this study juglone–loaded HSA nanoparticles targeted with LHRH peptide (jug-HSA-LHRH NPs) was prepared and evaluated for their anti-tumoural activity. Methods: The interaction between juglone and albumin was investigated and then, albumin nanoparticles were prepared based on an improved desolvation method. After preparation of juglone-loaded BSA nanoparticles, their anti-tumoural activity was evaluated on A431 and HT29 cells. Finally, juglone-loaded HSA nanoparticles (jug-HSA NPs) were prepared and targeted with LHRH. The anti-tumoural activity of jug-HSA-LHRH NPs was evaluated on T47D and SKOV3 cells as LHRH receptor positive and negative cells, respectively. Results: The fluorescence intensity of albumin was decreased in the presence of juglone by a static quenching mechanism. Van der Waals force and hydrogen bonding were the forces stabilizing the formation of complex and molecular docking results suggest IA site as the binding site. The nanoparticles preparation was simplified by using an apparatus for controlling the addition of ethanol and by using EDC, the time required for nanoparticles preparation was reduced to 3h. The enhanced cytotoxicity of juglone-loaded BSA nanoparticles was observed in both cell lines when compared to the free juglone and also BSA nanoparticles. The results did not show any differences between the uptake of targeted and non-targeted nanoparticles in the studied cancer cell lines. However, the cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were higher than that of non-targeted nanoparticles after 24 h of exposure. Discussion: Binding of juglone induces minimum conformational changes in protein. By using improved desolvation method, albumin nanoparticles of size around 100 nm were obtained. Albumin nanoparticles could be successfully used as a suitable and safe carrier for delivery of juglone.