The Preparation Of ROS Scavenging Polyoxometalate Nanoclusters For In Vivo Anti-inflammation

Reactive oxygen species(ROS),as one of the by-products of respiration,play important role in cell signaling and tissue homeostasis.The balance of ROS generation and elimination is necessary for metabolism.In some exogenous certain stimuli,overproduction of ROS in cells exceeding their ROS scavenging ability leads to oxidative stress that may disrupt a number of downstream pathological dysfunctions,such as inflammatory bowel disease(IBD)and neurodegenerative disorders.To avoid excessive ROS damaging the organism,anti-inflammatory drugs and natural antioxidants are usually used to solve the balance between ROS production and elimination.However,multi-symptom side effects(e.g.,gastrointestinal burden,off-target toxicity)were also recognized for anti-inflammation drugs or natural antioxidants.Recently,nanomaterials have been realized as a novel platform for the relief of oxidative stress targeting ROS scavenging mechanism because of the excellent physical and chemical properties.Liposomal ROS scavenging enzymes were successfully developed to treat IBD via intra-colonic administration.Although promising,the practical applications were still hindered by their intrinsic drawbacks,such as inducing immunological allergic reaction,susceptible to extreme p H as well as specific catalytic activity against just one among various ROS.Therefore,developing nanomaterials with multiple ROS scavenging capability,excellent stability and high biocompatibility is a promising strategy for alleviating oxidative stress-related diseases.In this research,ROS scavengable polyoxometalate nanoclusters were synthesized for safe and effective IBD preventative/therapeutic therapy.The main contents and results of this dissertation are described in two parts as below:1)W-based polyoxometalate nanoclusters(W-POM NCs)with uniform particle size and good dispersion were synthesized by imitating the Folin-Ciocalteu assay.The W-POM NCs possessed satisfactory scavenging ability to ROS including H₂O₂,O₂·^-,·OH and free radical due to charge transfer from reductive W⁵⁺to oxidated W⁶⁺.W-POM NCs had superior physiological stability and ROS elimination capabilities independent of dispersion medium,p H value and storage temperature,which attributed to the existence of hydrophilic gallic acid stabilizers.In cell experiments,W-POM NCs could be effectively phagocytized by NCM460 cells and showed great potential for eliminating intracellular ROS.2)Benefiting from the considerable X-ray absorbing property of W element,W-POM NCs with good stability and biosafety could be non-invasively monitored by clinical computed tomography(CT)after oral administration.W-POM NCs could successfully arrive at the inflamed region to recover colonic microstructures as evidenced by decreased ROS levels,Disease activity index(DAI)related pro-inflammatory cytokines and body weight loss in DSS-induced acute intestinal inflammation models,The considerable colitis preventative and therapeutic effects of W-POM NCs provide a valuable paradigm for safe and effective POMs-based IBD therapy.