Application Of 2D Metal Nanomaterials Based On Reactive Oxygen Species Modulation In Tumor And Inflammatory Disease

Reactive oxygen species(ROS),as oxygen-containing chemically active molecules,play an essential role in the cell signal transduction and homeostasis in living organisms.However,excessive ROS would lead to oxidative damage of the important components of cells.Therefore,the balance of intracellular ROS levels is closely related to the disease and life.It is well known that excess ROS would accumulate in inflamed tissues and further aggravate the inflammatory response.Thus,balancing oxidative stress in the inflamed tissues is an efficient strategy for treating inflammatory diseases.At the same time,utilizing ROS-mediated tumor treatment has been one of the hot topics in cancer therapy.In recent years,great efforts have been made in medicines centered on ROS generation and/or elimination for the treatment of various diseases.Due to their unique physic/chemical properties,two-dimensional(2D)metal compound nanomaterials,as a new kind of material,show great potential for biological application.Based on 2D metal nanomaterials to balance the oxidative stress,a satisfactory therapeutic effect can be achieved in the treatment of many diseases.Therefore,in this master dissertation,2D functional nanomaterials with excellent catalytic activity have been presented to generate or scavenge ROS for the treatment of tumors,inflammation,and other related diseases.The main research results of this dissertation are as follows:Firstly,reactive oxygen species play an important role in the physiological environment,and the redox imbalance can affect the metabolism,health status,disease,and so on.Therefore,balancing redox can be an important strategy for the treatment of diseases.In addition,the main mechanism of the current nanomaterials in generating or scavenging ROS,as well as the biological applications in anti-inflammatory and tumor therapy are summarized.Finally,the basis and research content of this thesis is presented.In the first project,titanium carbide nanosheets(Ti3C2 NSs)are developed as an oral dosage for the treatment of oxidative stress-induced inflammatory bowel disease(IBD).Ti3C2 NSs obtained by liquid-phase exfoliation have excellent ROS scavenging ability due to the strong reducibility of their Ti-C bonds,and have good stability in simulated gastric fluid.Cell experiments confirm that Ti3C2 NSs could effectively eliminate excess ROS and protect cells from oxidative stress damage.After oral administration,negatively-charged Ti3C2 NSs could adsorb to positively-charged inflamed colonic tissues through electrostatic interactions,thereby achieving an effective treatment for dextran sulfate sodium-induced colitis.Systematic therapeutic mechanism studies have shown that Ti3C2 NSs can reduce ROS levels and pro-inflammatory cytokine secretion,while increasing M2 phenotype macrophage infiltration and anti-inflammatory cytokine secretion,thereby effectively inhibiting inflammation and alleviating colitis symptoms.In addition,based on the excellent ROS scavenging ability,Ti3C2 NSs band-aid can be used to promote skin wound healing and the formation of functional blood vessels.Therefore,we develop a redox-mediated antioxidant nanoplatform as a novel oral nanomedicine for the treatment of IBD and other inflammatory diseases.In the second project,two-dimensional vanadium oxides are developed for sonodynamic-catalytic cancer therapy.Uniform-size vanadium-based hydroxide 2D nanosheets(HVO)are synthesized by a facile oxidation method based on V2H precursor.Due to a large number of oxygen vacancies in the HVO structure,it could trap e-under the ultrasound(US)irradiation to prevent the recombination of e-and h+,thereby enhancing sonodynamic effect.At the same time,due to the great catalytic properties of the V element,HVO nanosheets also have the horseradish peroxidase-like catalytic characteristics to catalyze the decomposition of hydrogen peroxide into ROS for further enhanced tumor treatment.In vitro and in vivo studies show that the prepared HVO nanosheets have achieved a good antitumor effect under US irradiation,and the mechanism of this combined therapy has also been studied.In summary,we have designed and synthesized different types of 2D functional nanosheets to adjust ROS levels(generate or scavenge ROS)for amplifying or eliminating ROS to achieve safe and efficient tumor or inflammatory diseases treatment.