Construction Of Self-assembled Hollow Nanomaterials And Study On Their Antioxidant Properties

Inspired by nature,such as DNA double helix structure,virus capsid structure,etc.,scientists have used tiny building blocks to build nanostructures of different shapes,sizes,and complexity by self-assembly.The building blocks use weak and reversible interactions or bonds to self-correct and self-correct under thermodynamically controlled conditions to form the most stable structures.The size and shape of different nanostructures play a decisive role in their functional performance.Therefore,people have begun to devote themselves to synthesizing nanostructured materials with specific morphology..Hollow nanomaterials with internal cavities and functionalized shells are potential candidates for biocatalysts due to their low mass density,large reactive specific surface area,high porosity,reduced charge transfer pathways,and good biocompatibility.Among the hollow nanomaterials,typical polymer nanocapsules and hollow metal-organic frameworks(Ho MOFs),have been widely used in catalysis,biomedicine,and other applications.However,for polymeric nanocapsules,their application potential is often limited by their synthesis methods,which usually require the synthesis of specific templates,tedious and complex polymerization,and de-templating processes.Therefore,scientists have proposed a more straightforward approach for the one-pot synthesis of polymer nanocapsules using planar rigid molecules with multiple reactive groups as the building blocks and cross-linking agents by covalent self-assembly.And there are also many problems in the preparation,the study of properties,and application of Ho MOFs.Therefore,the development of Ho MOFs and their composites with better properties and the elucidation of the relationship between their structures and reactions will make them more useful in a broader range of applications.Reactive oxygen species(ROS)such as superoxide anion radicals(O₂^·-),hydrogen peroxide(H₂O₂),and hydroxyl radicals(·OH)are closely related to a range of physiological and pathological processes in most organisms.Although proper ROS levels play a significant role in promoting the maintenance of normal physiological activities in the human body,excessive production of ROS can cause irreparable oxidative damage to lipids,proteins,and DNA.It can even induce various diseases such as inflammation or cancer in humans.For instance,in the therapy of cerebral infarction,the large amount of ROS produced due to ischemia-reperfusion(I/R)can lead to severe brain damage.Therefore,the exploitation of novel antioxidants with good antioxidant capacity using hollow nanomaterials has great application in the scavenging of reactive oxygen species and the therapy of cerebral infarction.By the above reflections,this thesis aims to construct novel hollow nanostructures and realize their morphological control and functionalization to develop nanomaterials with high antioxidant activity.1.Construction of polymer nanocapsules with tunable morphology based on dynamic covalent bondingSince the actual properties of nanomaterials depend on their morphology,it is particularly important to control their structure and morphology.Orthogonal dynamic covalent self-assembly is a simple method to construct polymeric hollow nanocapsules and thin films.In this part of work,we use 4-formylphenylboronic acid as a bifunctional precursor with symmetrically mounted boronic acid groups for cycloboroxane bonding and aldehyde groups for Schiff base reaction,which can be reacted with C2 symmetric linkers ethylenediamine and p-phenylenediamine to obtain polymeric nanocapsules and nanosheets,respectively.Due to the reversibility of the imine bonds,the morphological transformation between polymer nanocapsules and films can be successfully achieved by an amine-imine exchange strategy.Multiple reversible covalent bonds allow us to control the release of loading in polymer nanocapsules using different approaches.This has implications for the design of stimulus-responsive smart materials.2.Construction of a dual enzyme synergistic antioxidant system based on covalent self-assembled nanocapsulesDynamic reversible covalent bonds play a significant role in morphology modulation and controlled release.Still,the stability of the formed NCs decreases,while irreversible covalent bonds facilitate the construction of more stable nanocapsules,which will also contribute to the development of stable antioxidants.Manganese porphyrin derivatives can be used as SOD mimics capable of decomposing O₂^·-to H₂O₂ and O₂,and small molecules containing selenium can be used to mimic GPx,which subsequently decomposes H₂O₂ to H₂O and O₂.In this part of work,we have successfully constructed polymeric nanocapsules with SOD and GPx mimetic activities by a covalent self-assembly strategy using manganese porphyrin derivatives as the building blocks and selenium-containing diamine molecules as the cross-linkers,for mimicking natural multi-enzyme cascade antioxidant systems.In this system,the developed functional nanocapsules are highly biocompatible and have strong cellular internalization properties.Experimental results in vitro showed the scavenging effect and cytoprotective ability of this polymeric nanocapsule against ROS.This synthetic antioxidant model may contribute to our understanding of the role of natural antioxidants..3.Construction of a multi-enzyme synergistic antioxidant system based on selenium-containing hollow MOF and nanozymesDual enzyme cascade antioxidant systems have excellent performance in ROS scavenging and cytoprotection.Still,natural antioxidant systems generally consist of multiple enzyme systems,so the development of three or more antioxidant enzyme cascade systems will be more helpful in the treatment of ROS-related diseases.Cerebral ischemia-reperfusion injury(CIRI)is a secondary brain injury caused by explosive increase of ROS such as O₂^·-,H₂O₂,and·OH after restoration of blood supply to the brain,which may lead to deterioration of clinical neurological symptoms and even loss of neurological functions.To address this challenge,in this part of our work,we formed nanocomposites(Fe₂NC@Se)containing multiple antioxidant enzyme-mimicking activities by mimicking natural antioxidant systems and compounding Se-containing hollow MOFs with diatomic iron nanozymes by self-assembly.The atomically monodispersed diatomic iron nanozymes have the advantage of homogeneous active centers and high atom utilization efficiency,and exhibit higher SOD,CAT and OXD mimetic activities compared to monatomic iron nanozymes.DFT calculations show that the superior catalytic activity of Fe₂ clusters is attributed to synergistic effects,simplified rearrangement structures and lower key transition state energy differences.The Se-MOF shell layer,as a GPx mimetic also improved the stability and biocompatibility of the Fe₂NC nanozyme due to its positive electrical properties.In vitro and in vivo results suggest that the multifunctional antioxidant Fe₂NC@Se nanoparticles can inhibit oxidative damage in the brain and suppress neuronal apoptosis after CIRI by effectively eliminating intracellular ROS and potentially inhibiting the ASK/JNK apoptotic signaling cascade.This work opens a new avenue for the selection and design of antioxidant nanoparticles for enzymes that are expected to play an important role in the treatment of ischemic stroke.