Structural Effects of TiO2 Nanoparticles and Doxorubicin on DNA and their Antiproliferative Roles in T47D and MCF7 Cells

Azadeh      Hekmat; Ali   Akbar   Saboury; Adeleh      Divsalar; Arefeh      Seyedarabi

doi:10.2174/18715206113139990142

Abstract

The structural changes in DNA caused by the combined effects of TiO2 nanoparticles (TiO2 NPs) and doxorubicin (DOX) were investigated along with their corresponding inhibitory roles in the growth of T47D and MCF7 cells. The UV-visible titration studies showed that DOX+ TiO2 NPs could form a novel complex with DNA. The data also reveal that the TiO2–DOX complex forms through a 1:4 stoichiometric ratio in solution. The values of binding constants reveal that DOX+TiO2 NPs interact more strongly with DNA as compared to TiO2 NPs or DOX alone. CD data show that DOX+TiO2 NPs can noticeably cause disturbance on DNA structure compared to TiO2 NPs or DOX alone, considering that DNA is relatively thermally stable in the condition used. The anticancer property of 0.3 µM DOX+ 60 µM TiO2 NPs and 0.4 µM DOX+ 670 µM TiO2 NPs by MTT assay and DAPI stain demonstrates that this combination can tremendously diminish proliferation of T47D and MCF7cells compared to DOX or TiO2 NPs alone. The UV–Vis absorption spectroscopy, flow cytometry and fluorescence microscopy experiments show much more enhancement of DOX uptake through the use of TiO2 NPs. These results reveal that DOX+TiO2 NPs could proffer a novel strategy for the development of promising and efficient chemotherapy agents.

Keywords: Anthracycline, Anti-Cancer drug uptake, Breast cancer cell line T47D, Breast cancer cell line MCF7, Chemotherapeutic agent, Circular dichroism (CD), DAPI stain, DNA structure, Doxorubicin (Adriamycin), Drug combination, Flow cytometry, Fluorescence spectroscopy, Fluorescence microscopy, Human adult stem cell, MTT assay, Titanium dioxide nanoparticles (TiO2 NPs), UV-Visible spectroscopy.