Size dependent impact of platinum nanoparticles on doxorubicin activity

Abstract

Cancer is a leading cause of death worldwide, with nearly 10 million fatalities yearly. Consequently, despite the search for new therapeutic approaches, the use of classical chemotherapy, remains one of the main treatment regimens. Therefore, we evaluate the use of platinum nanoparticles (PtNPs) of different sizes as potential modulators of doxorubicin (DOX) activity.

In the presented research, we utilized a wide range of methods, including Spectroscopic measurements, Isothermal Titration Calorimetry, Dynamic Light Scattering, and Atomic Force Microscopy, as well as biological assays such as the Ames mutagenicity test on Salmonella enterica serovar Typhimurium TA98 and the alamarBlue cytotoxicity assay with Fluorescent Confocal Microscopy on non-cancerous HaCaT and cancerous MelJuSo cell lines, to investigate the interactions between PtNPs and DOX and the effect of diverse-sized nanoparticles on DOX activity.

The obtained results indicate the presence of direct interactions, particularly highlighting differences related to particles size. We confirmed that DOX affects the aggregation of nanoparticles, while the nanoparticles induce DOX fluorescence quenching. In terms of biological aspects, PtNPs reduced the mutagenicity of DOX, and increased the survival of non-cancerous HaCaT cells. Furthermore, 70 nm PtNPs significantly increased DOX effects on cancerous MelJuSo cells by negatively affecting their morphology and culture density.

To conclude, our research provided valuable insights into the interactions between PtNPs and DOX with particular emphasis on the nanoparticles’ size influence highlighting nanoparticles’ impact on DOX cytotoxicity providing a base for further research on the potential future modification in treatment approaches.