Platinum Nanoparticles as Modulators of Idarubicin Activity: A Physicochemical and In Vitro Biological Study.

Background/

Objectives

Cancer remains one of the leading causes of death worldwide. Although chemotherapy is widely used, it is associated with severe side effects, including myelosuppression and systemic toxicity. Nanoparticles have emerged as promising candidates for modulating drug activity. In this study, we investigated whether platinum nanoparticles (PtNPs) of various sizes interact with idarubicin (IDA), an anthracycline anticancer drug used primarily to treat acute leukaemia.

Methods

Interactions between PtNPs and IDA were analysed using dynamic light scattering (DLS), atomic force microscopy (AFM), fluorescence spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and near-infrared (NIR) spectroscopy. Thermodynamic and thermal properties were assessed using isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC). Biological effects were evaluated using the Ames mutagenicity assay on the Salmonella enterica serovar Typhimurium TA98 strain and cytotoxicity assays on SK-BR-3 and MCF-7 cell lines.

Results

DLS demonstrated changes in the hydrodynamic diameter of PtNPs following IDA addition, which were further supported by AFM imaging. PtNPs significantly quenched IDA fluorescence, indicating close molecular interactions, which were further supported by FTIR and NIR. ITC revealed that the interactions were endothermic, with enthalpy values ranging from 1.2 to 3.6 kcal/mol, and DSC demonstrated that the PtNP-IDA combination altered the melting temperature of IDA. Biological assays revealed that all examined PtNP sizes influenced IDA mutagenicity in the Salmonella enterica serovar Typhimurium TA98 strain. Furthermore, PtNPs modulated the cytotoxicity of IDA in SK-BR-3 and MCF-7 cell lines in a dose-dependent manner.

Conclusions

These findings demonstrate that PtNPs interact with IDA and modulate its biological activity. However, in this study no non-cancerous cell lines were examined; therefore, the observed interactions and biological effects support further investigation of the PtNP-IDA combination in the context of nanoparticle-assisted anticancer therapy on a broader range of in vitro cell lines.