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Multifunctional graphene quantum dots theragnostic agents for cancer therapy
Lee, Bong Han
Lee, Bong Han
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2023-07-28
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Despite the advancements of traditional methods for cancer therapy in treating some forms of disease, the heterogeneity of cancer and side-effects associated from the treatments have led to the emergence of novel therapeutic strategies. In this work, biocompatible bottom-up and top-down graphene quantum dots (GQDs) with visible and near-infrared fluorescence capability were tailored to function as photothermal agents with temperature sensing capabilities and delivery vehicles for CRISPR-Cas9, a gene editing tool, for anticancer treatment. In our work with photothermal therapy, GQDs irradiated with a low power 808 nm NIR laser have facilitated 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. GQDs facilitated the heating of HeLa cancer cells up to 54.5 °C, leading the drastic inhibition of cell viability from over 80% down to 22.9%. To probe temperature-sensitive processes at the nanoscale, GQDs also enabled biologically safe sub-cellular resolution sensing. Distinctive linear and reversible fluorescence quenching by up to 19.3% is observed for the visible and near-infrared GQD emission in aqueous suspension in the temperature range of 25 to 49 °C. A more pronounced trend is observed with GQD nanothermometers internalized into the cytoplasm of HeLa cells as they are tested in vitro from 25 °C to 45 °C with over 40% quenching response. In our work with gene therapy, GQDs and CRISPR-Cas9 RNP complex targeting the TP53 mutation overexpressed in ~50% of cancers successfully produces its double-stranded breaks in solution and in PC3 prostate cancer cells. Restoring this cancer “suicide” gene can promote cellular repair pathways and lead to cancer cell apoptosis. Its repair to the healthy form performed by simultaneous GQD delivery of CRISPR RNP and a gene repair template leads to a successful therapeutic outcome: 40% apoptotic cancer cell death, while having no effect on non-cancerous HeK293 cells. Overall, the combination of gene editing and photothermal therapy with temperature sensing modalities makes the GQDs developed in this work prospective agents for cancer theragnostics.
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Biophysics
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Physics and Astronomy