Automated Approach to In Vitro Image-Guided Photothermal Therapy with Top-Down and Bottom-Up-Synthesized Graphene Quantum Dots

Abstract

Graphene-based materials have been the subject of interest for photothermal therapy due to their high light-to-heat conversion efficiency. Based on recent studies, graphene quantum dots (GQDs) are expected to possess advantageous photothermal properties and facilitate fluorescence image-tracking in the visible and near-infrared (NIR), while surpassing other graphene-based materials in their biocompatibility. Several GQD structures including reduced graphene quantum dots (RGQDs) derived from reduced graphene oxide via top-down oxidation and hyaluronic acid graphene quantum dots (HGQDs) hydrothermally bottom-up synthesized from molecular hyaluronic acid were employed to test these capabilities in the present work. These GQDs possess substantial NIR absorption and fluorescence throughout the visible and NIR beneficial for in vivo imaging while being biocompatible at up to 1.7 mg/mL concentrations. In aqueous suspensions, RGQDs and HGQDs irradiated with a low power (0.9 W/cm2) 808 nm NIR laser facilitate a temperature increase up to 47.0 °C, which is sufficient for cancer tumor ablation. In vitro photothermal experiments sampling multiple conditions directly in the 96-well plate were performed using an automated simultaneous irradiation/measurement system developed on the basis of a 3D printer. In this study, HGQDs and RGQDs facilitated the heating of HeLa cancer cells up to 54.5 °C, leading to the drastic inhibition of cell viability from over 80% down to 22.9%. GQD’s fluorescence in the visible and NIR traces their successful internalization into HeLa cells maximized at 20 h suggesting both extracellular and intracellular photothermal treatment capabilities. The combination of the photothermal and imaging modalities tested in vitro makes the GQDs developed in this work prospective agents for cancer theragnostics.

Biocompatible Aluminum-Doped Graphene Quantum Dots for Dual-Modal Fluorescence and Ultrasound Imaging Applications

“…16 The red shift and broadness of this peak along with the extended absorption tail are attributed to surface defect states arising from oxygen, nitrogen, and aluminum dopants. 17,26 XPS in survey mode confirms the 3e), 34,35 where they are not present for GQDs without Al doping (Figure S2). This chemical and structural characterization suggests that Al-GQDs possess a graphitic platform with several oxygen-and nitrogen-containing functional groups modeled in Figure 3f.…”

“…The absorption spectrum of Al-GQDs presents several characteristic GQD features with a major peak centered at 275 nm (Figure a), representing the red-shifted π–π* electronic transition of the CC bond . The red shift and broadness of this peak along with the extended absorption tail are attributed to surface defect states arising from oxygen, nitrogen, and aluminum dopants. , XPS in survey mode confirms the presence of these dopants (Figure b), suggesting that Al-GQDs are composed of 66.0% carbon, 30.7% oxygen, 2.9% nitrogen, and 0.4% aluminum. High-resolution XPS (HR-XPS) scans at the C 1s, N 1s, and Al 2p peaks show their bound states.…”

“…Moreover, GQD structures can be synthetically tailored to facilitate specific therapeutic functions, such as targeting disease sites, 24 delivering drug and gene medicine, 25 and assisting with photothermal ablation. 26 Based on the apparent advantageous properties of metal-doped GQD structures, we propose the synthesis of biocompatible aluminum-doped GQD (Al-GQD) delivery vehicles as potential adjuvants in order to test their fluorescence tracking and ultrasound imaging capabilities.…”

“…Incorporating metal dopants into the GQD platform also produces biocompatible nanostructures with additional ultrasound contrast capablities. − Such multimodality is enabled by a simple and scalable bottom-up GQD synthesis from the plethora of carbonaceous precursor materials. Moreover, GQD structures can be synthetically tailored to facilitate specific therapeutic functions, such as targeting disease sites, delivering drug and gene medicine, and assisting with photothermal ablation . Based on the apparent advantageous properties of metal-doped GQD structures, we propose the synthesis of biocompatible aluminum-doped GQD (Al-GQD) delivery vehicles as potential adjuvants in order to test their fluorescence tracking and ultrasound imaging capabilities.…”

Editorial for Special Issue: “Supramolecular Nanomaterials for Biomedical Application”

“…Considering that graphene-based nanomaterials can facilitate the process of neurogenesis in vitro, using different microscopy techniques and real-time gene-expression analysis, Simonovic et al explored the ability of liquid-phase-exfoliated graphene films to induce and stimulate the neural differentiation of stem cells from apical papilla (SCAP) [ 12 ]. Lee et al utilized simple and scalable top-down and bottom-up approaches to prepare reduced-graphene quantum dots (RGQDs) and hyaluronic acid–graphene quantum dots (HGQDs), which possessed substantial near-infrared (NIR) absorption and fluorescence throughout the visible and NIR ranges, showing significant photothermal performance as well as NIR and fluorescence-imaging capabilities in HeLa cells [ 13 ]. Bahutair et al reviewed the recent applications of ultrasound-stimulated drug release from liposomal systems, stated the various factors affecting the sonosensitivity of liposomes and the mechanisms of ultrasound-stimulated drug release, and finally summarized the studies of ultrasound-induced liposome smart-drug-delivery systems (SDDSs) in vitro and in vivo [ 14 ].…”