Revealing the interaction strategy of Diosmin functionalized gold nanoparticles with ctDNA: Multi-spectroscopic, calorimetric and thermodynamic approach

Abstract

The interactions of natural drug functionalized metal nanoparticles with DNA plays a pivotal role in developing effective therapeutic agents having a wide range of potential biomedical applications. The focus of this study was to decipher the binding mechanism of diosmin capped gold nanoparticles (DM-AuNPs) with calf thymus DNA (ctDNA) through a combination series of spectroscopic and calorimetric studies. The gold nanoparticles were successfully synthesized by the facile one-pot synthesis using DSM as a capping and reducing agent. The DM-AuNPs were characterized using UV–Visible spectroscopy, XRD, FTIR, DLS and HRTEM analysis confirming the formation of stable AuNPs with an average size of 30 ± 3 nm. A series of experiments such as UV–Vis absorbance, fluorescence dye displacement studies, temperature melting and viscosity analysis unravelled the binding mode of DM-AuNPs by establishing a typical groove binding mode upon its complexation with ctDNA. The CD and FTIR measurements provided clear-cut evidences regarding the conformational alterations and the stability of ctDNA double helical structure in the presence of DM-AuNPs. The thermodynamic binding parameters deduced from the ITC revealed that the binding was exothermic and spontaneous in nature. All these results maintained consistency with the typical groove binding fashion of DM-AuNPs and confirmed the formation of DM-AuNPs-ctDNA complex. The MTT assay revealed a moderate anti-proliferative and toxicity effects of DM-AuNPs on MCF-7 and normal human cell lines. In this context the entire results based on ctDNA-DM-AuNPs binding mechanism may facilitate sensible synthesis and designing of various synthetic/natural drug functionalized nanoparticles possessing better therapeutic and sensing efficacy with minimal toxicity.