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

Titanium dioxide nanoparticles (TiO₂ NPs) have been proven to be potential candidates in cancer therapy, particularly photodynamic therapy (PDT). However, the application of TiO₂ 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, TiO₂ NPs and N-doped graphene quantum dots (QDs)/titanium dioxide nanocomposites (N-GQDs/TiO₂ NCs) were synthesized via microwave-assisted synthesis and the two-pot hydrothermal method, respectively. The synthesized anatase TiO₂ NPs were self-doped TiO₂ (Ti³⁺ ions), have a small crystallite size (12.2 nm) and low bandgap energy (2.93 eV). As for the N-GQDs/TiO₂ 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/TiO₂ NCs with near-infrared (NIR) light, the nanocomposites generated reactive oxygen species (ROS), mainly singlet oxygen (¹O₂), 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/TiO₂ 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.