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.

Nanomedicine-Based Strategies Assisting Photodynamic Therapy for Hypoxic Tumors: State-of-the-Art Approaches and Emerging Trends.

Since the first clinical cancer treatment in 1978, photodynamic therapy (PDT) technologies have been largely improved and approved for clinical usage in various cancers. Due to the oxygen-dependent nature, the application of PDT is still limited by hypoxia in tumor tissues. Thus, the development of effective strategies for manipulating hypoxia and improving the effectiveness of PDT is one of the most important area in PDT field. Recently, emerging nanotechnology has benefitted progress in many areas, including PDT. In this review, after briefly introducing the mechanisms of PDT and hypoxia, as well as basic knowledge about nanomedicines, we will discuss the state of the art of nanomedicine-based approaches for assisting PDT for treating hypoxic tumors, mainly based on oxygen replenishing strategies and the oxygen dependency diminishing strategies. Among these strategies, we will emphasize emerging trends about the use of nanoscale metal-organic framework (nMOF) materials and the combination of PDT with immunotherapy. We further discuss future perspectives and challenges associated with these trends in both the aspects of mechanism and clinical translation.

Electronic structure manipulation of graphene dots for effective hydrogen evolution from photocatalytic water decomposition.

This paper presents a heteroatom doping strategy to manipulate the structure of graphene-based photocatalysts for effective hydrogen production from aqueous solution. Oxygenation of graphene creates a bandgap to produce semiconducting graphene oxide, nitrogen doping extends the resonant π-conjugation to prolong the charge lifetime, and sulfur doping breaks the electron neutrality to facilitate charge transfer. Accordingly, ammonia-treated sulfur-nitrogen-co-doped graphene oxide dots (A-SNGODs) are synthesized by annealing graphene oxide sheets in sulfur-ammonia, oxidizing the sheets into dots, and then hydrothermally treating the dots in ammonia. The A-SNGODs exhibit a high nitrogen content in terms of quaternary and amide groups that are formed through sulfur-mediated reactions. The peripheral amide facilitates orbital conjugations to enhance the photocatalytic activity, whereas the quaternary nitrogen patches vacancy defects to improve stability. The simultaneous presence of electron-withdrawing S and electron-donating N atoms in the A-SNGODs facilitates charge separation and results in reactive electrons. When suspended in an aqueous triethanolamine solution, Pt-deposited A-SNGODs demonstrate a hydrogen-evolution quantum yield of 29% under monochromatic 420 nm irradiation. The A-SNGODs exhibit little activity decay under 6-day visible-light irradiation. This study demonstrates the excellence of the heteroatom-doping strategy in producing stable and active graphene-based materials for photoenergy conversion.