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

Pravena Ramachandran,Boon-Keat Khor,Nguyen Thi Kim Thanh,Chern Ein Oon,Ruey-An Doong,Chong Yew Lee,Hooi Ling Lee

doi:10.3390/biomedicines10020421

Pravena Ramachandran, Boon-Keat Khor + Show 5 more

Open Access

https://doi.org/10.3390/biomedicines10020421

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Abstract

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.

Highlights

In recent years, scientists have focused on nanoparticle research in the biomedical field, in cancer therapies
The obtained findings suggest that the structure and phase purity of TiO2 remained intact, as N-GQDs were incorporated on the surface of the TiO2, and not into the TiO2 lattice
This work reports the successful synthesis of TiO2 conjugated with N-GQDs via the Thishydrothermal work reports the successful synthesis

Summary

Introduction

Scientists have focused on nanoparticle research in the biomedical field, in cancer therapies. Biomedicines 2022, 10, 421 can play multiple roles, as they can be used for diagnosis and therapy simultaneously. Metal or metal oxide nanoparticles can generate ROS in the presence of light illumination to induce cell death [2,3]. Acting as a photosensitizer or nanocarrier, metal oxides exhibit relatively good stability when compared to existing organic nanoparticles (liposomes, dendrimers, polymer-based NPs), with regard to temperature and pH change [4,5]. An optical irradiation-induced generation of ROS by a photosensitizer that promotes cell killing is known as photodynamic therapy (PDT). PDT is an emerging non-invasive, clinically approved and localized therapy for several diseases, including cancers. PDT surpasses existing traditional cancer treatments as it can be targeted, is noninvasive, causes negligible drug resistance and is highly effective with fewer adverse side effects [6]

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