Concise nanotherapeutic modality for cancer involving graphene oxide dots in conjunction with ascorbic acid.

Cancer cells tend to have higher intracellular reactive oxygen species (ROS) levels and are more vulnerable to ROS-generating therapies such as ascorbic acid (H2Asc) therapy, whose potency has been explored by several clinical trials. However, its efficiency is restricted by the requirement of pharmacologically high local H2Asc concentrations. Here, we show that nitrogen-doped graphene oxide dots (NGODs), which are highly crystalline and biocompatible, can serve as a catalytic medium for improving H2Asc cancer therapy at orally achievable physiological H2Asc concentrations. NGODs catalyze H2Asc oxidation for H2O2 and dehydroascorbic acid generation to disrupt cancer cells by consuming intracellular glutathione (GSH) and inducing ROS damage. This is the first study to demonstrate the direct consumption of GSH using a carbon-based nano-catalyst (NGODs), which further expedites tumor killing. In addition, as in our previous study, NGODs can also serve as a highly efficient photosensitizer for photodynamic therapy. Under illumination, NGODs produce a considerable amount of H2O2 in the presence of physiological levels of H2Asc as a hole scavenger and further enhance the therapeutic efficiency. Thus, a concise nanotherapeutic modality could be achieved through the conjunction of multifunctional NGODs and H2Asc to selectively eliminate deep-seated and superficial tumors simultaneously (under 65% of normal cell viability, it kills almost all cancer cells). Note that this level of therapeutic versatility generally requires multiple components and complex manufacturing processes that run into difficulties with FDA regulations and clinical applications. In this study, the concise NGOD-H2Asc nanotherapeutic modality has demonstrated its great potential in cancer therapy.

Biocompatible hole scavenger-assisted graphene oxide dots for photodynamic cancer therapy.

Photodynamic therapy (PDT) receives scholarly attention for its low invasiveness and mild adverse effects. Among the reactive oxygen species for PDT, H2O2 is advantageous for achieving long life and low cytotoxicity. Nitrogen-doped graphene oxide dots (NGODs), which are small (∼4.4 nm) and highly biocompatible, can serve as a photosensitizer for PDT. The charge transfer in NGODs is efficient because the NGOD structure is highly crystalline and its carbon-π orbitals are extensively conjugated with nitrogen-nonbonding orbitals. In the presence of ascorbic acid (AA), to scavenge photogenerated holes, NGODs effectively produce H2O2 under white-light irradiation and their H2O2 rate is proportional to the AA concentration. This AA-supplemented PDT effectively kills lung, head and neck, colon, and oral cancer cells and it is highly safe for normal cells. During PDT, the NGODs are uptaken into the cell body and they produce concentrated H2O2 and subsequently induce both the apoptosis and necrosis pathways for cell death. The unique structure of NGODs confines the transfer of the photogenerated electrons for H2O2 production. This study demonstrates the high potential for efficacious and accurate deployment of the proposed NGOD-AA combination in PDT.

Elucidating Quantum Confinement in Graphene Oxide Dots Based On Excitation-Wavelength-Independent Photoluminescence.

Investigating quantum confinement in graphene under ambient conditions remains a challenge. In this study, we present graphene oxide quantum dots (GOQDs) that show excitation-wavelength-independent photoluminescence. The luminescence color varies from orange-red to blue as the GOQD size is reduced from 8 to 1 nm. The photoluminescence of each GOQD specimen is associated with electron transitions from the antibonding π (π*) to oxygen nonbonding (n-state) orbitals. The observed quantum confinement is ascribed to a size change in the sp(2) domains, which leads to a change in the π*-π gap; the n-state levels remain unaffected by the size change. The electronic properties and mechanisms involved in quantum-confined photoluminescence can serve as the foundation for the application of oxygenated graphene in electronics, photonics, and biology.