Controllable Synthesis And Antioxidant Activity Investigation Of Ultrasmall Polydopamine Nanodots And Their Application In The Treatment Of Colitis

As a kind of nanomaterials with efficient scavenging ability towards reactive oxygen species(ROS)and reactive nitrogen species(RNS),antioxidant nanomaterials have been widely used in various biomedical fields due to their convenient construction,low cost,and high biological safety.Though promising,their biological usage and medical transformation are often limited by their formulation design and antioxidant efficiency.In this dissertation,we synthesized novel ultra-small polydopamine-based dots(PDA dots),as well as explored their broad-spectrum ROS and RNS scavenging ability.Both in vivo and in vitro toxicity studies confirmed that these nanoantioxidants exhibited high biocompatibility.Dextran sulfate sodium salt(DSS)-induced ulcerative colitis was used as an animal model to investigate the antioxidant effect of our oral preparation of PDA dots.Detailed experimental results are summarized as follows.(1)PDA dots with an average size of 3 nm were obtained by using a facile one-step hydrothermal synthesis.A variety of ROS and RNS free radicals were selected and used to explore their antioxidant capacity and free radical scavenging capacity.Compared with the previously reported PDA NPs with an average size of 160 nm,current experimental results indicated that PDA dots and PDA NPs held similar chemical structure,and PDA dots revealed better free radical scavenging ability,similar to small molecule dopamine.(2)Both in vitro and in vivo toxicity of these newly developed PDA dots was well evaluated.Experimental results based on cytotoxicity,blood compatibility,and oral long-term toxicity demonstrated that these PDA dots showed high biosafety.(3)Oxidative damage cell model and DSS-induced ulcerative colitis animal model were successfully constructed,and the antioxidant effect of these PDA dots was investigated in detail.Experimental results indicated that these novel PDA dots could alleviate the level of antioxidant enzymes in cells or tissues and reduce the degree of lipid peroxidation by scavenging ROS and RNS,so as to achieve admirable antioxidant therapy both in vivo and in vitro.