Platinum nanoparticles interact with epirubicin in size dependent manner and affect its biological activity

In 2022, nearly 20 million new cancer cases were diagnosed worldwide. Despite undeniable improvement in cancer treatment, chemotherapy, a frequently used method, remains limited due to severe side effects. Hence, in this research we utilized platinum nanoparticles (PtNPs) of varying sizes to investigate their interactions with epirubicin (EPI), a commonly used anticancer drug, and asses their impact on its biological activity. We employed various physicochemical methods, including Fluorescence and Infrared Spectroscopies, Differential Scanning Calorimetry, Isothermal Titration Calorimetry, Atomic Force Microscopy and Dynamic Light Scattering with Zeta Potential measurements, to investigate the interactions and aggregation patterns of PtNPs with EPI. Moreover, the biological effect of these interactions, with a particular emphasis on the differences due to nanoparticles' sizes, was verified in Ames mutagenicity test on Salmonella enterica serovar Typhimurium TA98 and through cytotoxicity assays on MelJuSo (cancerous) and HaCaT (non-cancerous) cell lines. The obtained results confirmed the presence of PtNPs-EPI interactions depending on the nanoparticles' size. The physicochemical analyses revealed the formation of EPI-induced aggregates of nanoparticles, which may be of great importance in the context of the biological effects. Consequently, the biological part indicated that PtNPs decrease EPI mutagenicity and increase its cytotoxicity in cancerous cell line. In the contrary, nanoparticles exhibited a potential protective effect on cells and mostly increased or maintained the cells viability in non-cancerous cell line. Summing up, our research provides valuable insights into the PtNPs influence on epirubicin with special focus on the differences attributed to nanoparticles sizes.