Synthesis and Study of the Photodynamic Activity of Titanium-based Nanocomposites on MDA-MB-231 Cells

Abstract

Breast cancer is the most common prevalent cancer in women, and the second main cause of cancer death in women, after lung cancer. Among the emerging cancer therapy methods, photodynamic therapy (PDT) with titanium dioxide nanoparticles (TiO2 NPs) as photosensitizing agent has gained great interest due to its high efficiency. However, its application for PDT is limited due to its wide bandgap $(\sim 3.2eV)$, which can only be excited by ultraviolet irradiation. In this study, TiO2 NPs conjugated with N-doped graphene quantum dots composites ($N-GQDs/TiO_{2}$ NCs) were successfully prepared by the two-pot hydrothermal method. The synthesized nanocomposites were characterized by Ultraviolet-visible Diffuse Reflectance spectrophotometer (UVDRS), high-resolution transmission electron microscopy (HRTEM) and X-ray powder diffraction (XRD). The results exhibited that TiO2 particles were located on the surface of the 2-D graphene nanosheets in $N-GQDs/TiO_{2}$ NCs $(9-11nm)$ with high crystallization. Dispersion of NCs in cell culture were studied prior to cytotoxicity assay and PDT. Dispersing this NCs in Dulbecco’s modified eagle’s medium (DMEM) with 1% fetal bovine serum (FBS) $(86.8\pm 4.3nm)$ resulted in smaller hydrodynamic size as compared to DMEM without FBS (679.9 $\pm 3.7nm)$ and deionized water (DI water) $(203.5\pm 4.8nm)$. Cytotoxicity assay was tested using 0. 01-1 mg/mL of N-GQDs/TiO2 NCs for 24 h without light irradiation. The initial cell viability study presents the safe concentration was from 0.01 mg/mL to 0.5 mg/mL as viability decreased prominently at 1.0 mg/mL. The $N-GQDs/TiO_{2}$ NCs were photo-activated with infrared light which has better penetrability in deeper locations in the breast tissue due to their nano-scale size. Upon photo-activation, the nanocomposites generate reactive oxygen species (ROS) that cause cell death in MDA-MB-231 breast cancer cells. At constant light energy $(20J/cm^{2})$, increasing N-GQDs/TiO2 NCs concentrations led to the increased intracellular ROS levels that elevated cell death rate in MDAMB-231 cells. The results suggested $N-GQDs/TiO_{2}$ NCs as a potential PDT photosensitizing agent with infrared irradiation.