N-Doped Graphene Quantum Dots/Titanium Dioxide Nanocomposites: A Study of ROS-Forming Mechanisms, Cytotoxicity and Photodynamic Therapy

Titanium dioxide nanoparticles (TiO(2) NPs) have been proven to be potential candidates in cancer therapy, particularly photodynamic therapy (PDT). However, the application of TiO(2) NPs is limited due to the fast recombination rate of the electron (e(−))/hole (h(+)) pairs attributed to their broader bandgap energy. Thus, surface modification has been explored to shift the absorption edge to a longer wavelength with lower e(−)/h(+) recombination rates, thereby allowing penetration into deep-seated tumors. In this study, TiO(2) NPs and N-doped graphene quantum dots (QDs)/titanium dioxide nanocomposites (N-GQDs/TiO(2) NCs) were synthesized via microwave-assisted synthesis and the two-pot hydrothermal method, respectively. The synthesized anatase TiO(2) NPs were self-doped TiO(2) (Ti(3+) ions), have a small crystallite size (12.2 nm) and low bandgap energy (2.93 eV). As for the N-GQDs/TiO(2) NCs, the shift to a bandgap energy of 1.53 eV was prominent as the titanium (IV) tetraisopropoxide (TTIP) loading increased, while maintaining the anatase tetragonal crystal structure with a crystallite size of 11.2 nm. Besides, the cytotoxicity assay showed that the safe concentrations of the nanomaterials were from 0.01 to 0.5 mg mL(−1). Upon the photo-activation of N-GQDs/TiO(2) NCs with near-infrared (NIR) light, the nanocomposites generated reactive oxygen species (ROS), mainly singlet oxygen ((1)O(2)), which caused more significant cell death in MDA-MB-231 (an epithelial, human breast cancer cells) than in HS27 (human foreskin fibroblast). An increase in the N-GQDs/TiO(2) NCs concentrations elevates ROS levels, which triggered mitochondria-associated apoptotic cell death in MDA-MB-231 cells. As such, titanium dioxide-based nanocomposite upon photoactivation has a good potential as a photosensitizer in PDT for breast cancer treatment.