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

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.

Sensitive detection of trace level Cd (II) triggered by chelation enhanced fluorescence (CHEF) "turn on": Nitrogen-doped graphene quantum dots (N-GQDs) as fluorometric paper-based sensor.

Cadmium ion (Cd (II)) is a highly toxic heavy metal usually found in natural water. Exposure to Cd (II) can produce serious effects in human organs such as Itai-Itai disease. Therefore, the maximum allowance levels of Cd (II) in drinking water and herbal medicines imposed by the World Health Organization (WHO) are 3 µg L-1 and 300 µg kg-1, respectively. In this work, nitrogen-doped graphene quantum dots (N-GQDs) as a fluorescent sensor for Cd (II) determination was developed in both solution-based and paper-based systems. N-GQDs were synthesized from citric acid (CA) and ethylenediamine (EDA) via the hydrothermal method. The synthesized N-GQDs emitted intense blue fluorescence with a quantum yield (QY) of up to 80%. The functional groups on the surface of N-GQDs measured by FTIR were carboxyl (COO-), hydroxyl (OH-), and amine (NH2) groups, suggesting that they could be bound to Cd (II) for complexation. The fluorescence intensity of N-GQDs was gradually enhanced with the increase of Cd (II) concentration. This phenomenon was proved to result from the fluorescence enhancement (turn-on) based on the chelation enhanced fluorescence (CHEF) mechanism. Under the optimum conditions in the solution-based and paper-based systems, the limits of detection (LODs) were found to be 1.09 and 0.59 µg L-1, respectively. Furthermore, the developed sensors showed relatively high selectivity toward Cd (II) over ten other metal cations and six other anions of different charges. The performance of the sensor in real water and herbal medicine samples exhibited no significant difference as compared to the results of the validation method (ICP-OES). Therefore, the developed sensors can be used as fluorescent sensors for Cd (II) determination with high sensitivity, high selectivity, short incubation time (5 min). As such, the paper-based strategy has excellent promising potential for practical analysis of Cd (II) in water and herbal medicine samples with a trace level of Cd (II) concentrations.

A titanium dioxide/nitrogen-doped graphene quantum dot nanocomposite to mitigate cytotoxicity: synthesis, characterisation, and cell viability evaluation.

Titanium dioxide nanoparticles (TiO2 NPs) have attracted tremendous interest owing to their unique physicochemical properties. However, the cytotoxic effect of TiO2 NPs remains an obstacle for their wide-scale applications, particularly in drug delivery systems and cancer therapies. In this study, the more biocompatible nitrogen-doped graphene quantum dots (N-GQDs) were successfully incorporated onto the surface of the TiO2 NPs resulting in a N-GQDs/TiO2 nanocomposites (NCs). The effects of the nanocomposite on the viability of the breast cancer cell line (MDA-MB-231) was evaluated. The N-GQDs and N-GQDs/TiO2 NCs were synthesised using a one- and two-pot hydrothermal method, respectively while the TiO2 NPs were fabricated using microwave-assisted synthesis in the aqueous phase. The synthesised compounds were characterised using Fourier transform infrared (FTIR) spectroscopy, high-resolution transmission electron microscopy (HRTEM), field emission scanning electron microscopy (FESEM) and UV-visible spectrophotometry. The cell viability of the MDA-MB-231 cell line was determined using a CellTiter 96® AQueous One Solution Cell Proliferation (MTS) assay. The obtained results indicated that a monodispersed solution of N-GQDs with particle size 4.40 ± 1.5 nm emitted intense blue luminescence in aqueous media. The HRTEM images clearly showed that the TiO2 particles (11.46 ± 2.8 nm) are square shaped. Meanwhile, TiO2 particles were located on the 2D graphene nanosheet surface in N-GQDs/TiO2 NCs (9.16 ± 2.4 nm). N-GQDs and N-GQDs/TiO2 NCs were not toxic to the breast cancer cells at 0.1 mg mL-1 and below. At higher concentrations (0.5 and 1 mg mL-1), the nanocomposite was significantly less cytotoxic compared to the pristine TiO2. In conclusion, this nanocomposite with reduced cytotoxicity warrants further exploration as a new TiO2-based nanomaterial for biomedical applications, especially as an anti-cancer strategy.