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.

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.