The cytotoxic effects of nanoparticles encapsuled combination of doxorubicin and epoxomicin on breast cancer cells

Objective: Delivery of chemotherapeutic drugs encapsulated in the nanoparticles (NPs) directly to the tumors has been used in breast cancer. This way, cytotoxic effects of drugs are reduced on normal cells and drug resistance is inhibited in cancer cells. In our study, we synthesized NPs encapsulating chemotherapeutics and investigated their cytotoxic effects on cancer and normal cells. Method: Doxorubicin (Dox) and/or Epoxomicin (Epo) loaded Poly(lactic-co-glycolic acid) (PLGA) NPs were prepared using a modified o/o/w double emulsion phase separation method. Physicochemical properties of the synthesized NPs were performed using size analysis and zeta potential with zetasizer, particle morphology with scanning electron microscopy (SEM), weight loss with thermogravimetric analysis (TGA), energy change with differential scanning calorimetry (DSC), and chemical bonds analysis with fourier transform infrared spectroscopy (FTIR). Furthermore, the effects of synthesized NPs on cytotoxicity, apoptosis, apoptotic pathways, and drug resistance were investigated in vitro in cell cultures models created using breast cancer cells (MCF-7) and normal cells (HUVEC). Results: The presence of Dox and/or Epo within NPs was proven by these material characterization analyses, revealing that Dox and/or Epo could be successfully loaded into the nanoparticles. Dox and Epo loaded NPs are more cytotoxic than free Dox and Epo to MCF-7 cells while they are less cytotoxic than free Dox and Epo to normal HUVEC cells. As a result, Dox and Epo-loaded NPs reduced drug resistance and increased the cytotoxicity, apoptosis, and activation of apoptotic pathways in MCF-7 cells. Conclusion: Clinical projects applying nanoparticles encapsulating drug combinations (Dox and/or Epo) might be carried out as a potential treatment to overcome multidrug resistance and toxicity to normal tissues.