The effect of platinum nanoparticles on the physicochemical properties of daunorubicin

Abstract

Cancer is a difficult disease to cure due to its diversity and complexity. Despite novel therapeutic approaches having been proposed in recent years, chemotherapy remains one of the most common treatment regimens to this day. Unfortunately, its anticancer effects are often quelled by the lack of selectivity; hence alteration of the activity of already existing drugs by combining them with potential modulators e.g. metallic nanoparticles has been proposed as a possible strategy to overcome this problem. Herein, we verified if platinum nanoparticles (PtNPs) of various sizes interact with daunorubicin (DAU), a chemotherapeutic agent used for the treatment of leukaemia. Utilizing DLS and NTA we observed nanoparticle aggregation upon addition of increasing concentrations of DAU. Furthermore, we noticed that PtNPs quench DAU's fluorescence, suggesting their direct interaction. Next, we used FTIR and NIR spectroscopies and registered significant changes in the obtained spectra in the presence of PtNPs. The ITC and DSC analyses showed that all tested sizes of PtNPs interact with DAU in an endothermic manner, with the enthalpy change between 0.47 and 4.36 kcal mol⁻¹. The release analysis employing the dialysis bag method evidenced that PtNPs influence DAU's diffusion kinetics, decreasing its release from 100% (when alone) to ca. 70% when combined with PtNPs. All tested sizes of PtNPs reduce DAU's mutagenicity towards S.enterica serovar Typhimurium TA98 strain, however, no significant influence on DAU's cytotoxicity was observed on neither MelJuSo nor HaCaT eukaryotic cell lines. Overall, these results indicate that PtNPs may affect DAU's biological activity and warrant further biological studies.