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

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/cm(2)) 808 nm NIR laser facilitate a temperature increase up to 47.0 degrees 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 degrees 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.

Automated summary

Graphene quantum dots (GQDs) show high light-to-heat conversion efficiency and excellent biocompatibility, making them promising for photothermal therapy. In this study, GQDs such as reduced graphene quantum dots (RGQDs) and hyaluronic acid graphene quantum dots (HGQDs) were tested and proved to have substantial NIR absorption and fluorescence, allowing for in vivo imaging and tumor ablation. The experiments conducted using HeLa cancer cells demonstrated that GQDs can heat the cells up to 54.5°C and significantly inhibit cell viability. The fluorescence of GQDs indicates their successful internalization into the cells, suggesting their potential as cancer theragnostics agents.