Insights about the interaction of methotrexate loaded hydrophilic gold nanoparticles: spectroscopic, morphological and structural characterizations

Gold nanoparticles (AuNPs) are promising carriers in the field of nanomedicine and represent a very intriguing approach in drug delivery applications, due to their small size and enhanced properties. This work aims to highlight the interaction between functionalized AuNPs and the immune-system suppressant drug Methotrexate (MTX) at molecular level. Small and monodisperse (<2RH>5 ± 1 nm) gold nanoparticles were prepared by a simple chemical route using hydrophilic thiol 3-mercapto-1-propanesulfonate (3MPS) as a functionalizing/ capping agent and act as a platform for post-synthesis conjugation of MTX via non-covalent interaction. The AuNPs-3MPS@MTX bioconjugate and the AuNPs alone were characterized to investigate their optical, chemical, and morphological properties. Moreover, NMR, AFM, SAXS, HR-TEM and SR-XPS data confirmed the spherical shape of AuNPs and allowed to determine the mechanisms behind such drug-nanoparticle physicochemical interactions. These analyses define the overall structure of drug-loaded AuNPs-3MPS and drug location on the colloidal nanoparticles surface. Based on the experimental data, it is notable to assert that MTX was successfully loaded on the negatively charged nanoparticles surface via electrostatic interactions. The physicochemical behavior leads to the formation of large clusters with close packed arrangement of AuNPs-3MPS@MTX. This selfassembling property is of importance for delivery purpose affecting the drug-loaded nanoparticle size, functionality, and morphology. Knowledge of how these systems behave will aid in increasing drug efficacy and in understanding the pharmacodynamics and pharmacokinetic properties, opening to new physicochemical insight for therapy and drug delivery systems.