Design of New-Generation Nanozymes for Biomedical Application

Author:Cao Fang Fang

Supervisor:ren jin song


Degree Year:2019





Nanozymes,nanomaterials with biocatalytic activities,has successfully mimicked natural enzymes and been used in various fields.Although they overcome the innate drawbacks of natural enzymes,such as complex preparation,high cost,poor stability and low recycling efficiency,nanozymes still face enormous challenges.Specifically,their bioapplication are severely restricted by the low catalytic activity,poor specificity and selectivity,lack of targeting capacity,undefined catalytic mechanism as well as ambiguous active structure.Here,fouced on the challenges of nanozymes,we first designed a series of nanozymes to enhance their application in various fields such as cancer treatment,bacterial elimination and antioxidant therapy.Meanwhile,we also increase the bioactivities and reduce the potential biotoxicities of silver nanoparticles(AgNPs)for use in the related biomedical fields.The main results are summarized as follows:1.Generally,shrinking the sizes of nanozymes can generate a large active surface area for catalytic reactions in various practical usages.However,the concomitant increase of surface free energy will intensify the risk of nanozymes’aggregation and further cause the loss of the catalytic ability.To overcome these limitations,we rationally design and fabricate uniformly dispersed ultrasmall nanozymes(CeO2 NSs)for the first time by using well-ordered crystalline metal organic frameworks(MOFs)as precursors in this study.As expected,excellent characters of these MOF-derived CeO2 NPs including oxidase-like activity,ATP deprivation capacity,and porous structure endow them with admirable oxidative damage effect,specially reduced energy supply ability,and high drug loading capacity.Both in vitro and in vivo results indicate the great promise of these well-prepared nanostructures in synergistic cancer therapy with negligible side effects.2.With intrinsic catalytic activities,nanozymes have emerged as a new generation of "antibiotics" with exciting broad-spectrum antimicrobial potencies and negligible biotoxicities.However,their antibacterial efficacies are still far from satisfactory due to the lack of bacterial capturing capacity and relatively lower catalytic activity.Herein,for the first time,we report a one-step strategy to simultaneously promote the binding capacity and catalytic activity of nanozymes by constructing rough surfaces with exposed defect-rich active edges,as firstly investigated experimentally and theoretically.A significantly higher bacterial capturing capacities and antibacterial efficacies against drug-resistance Gram-negative E.coli and Gram-positive S.aureus both in vitro and in vivo are obtained in such efficient nanozymes.3.Sepsis,characterized by immoderate production of multiple reactive oxygen and nitrogen species(RONS),continues to cause high morbidity and mortality worldwide.Despite the progress made with nanozymes,the efficient antioxidant therapy that could fast eliminate all of these RONS remains challenging,owing largely to the specificity and low activity of exploited nanozymes.Herein,we report a novel single-atom-enzyme,Co/PMCS,featuring with atomically dispersed coordinatively unsaturated active Co-porphyrin centers,can fast obliterate multiple RONS to alleviate sepsis,that can defeat nanozymes.Eventually,it can reduce proinflammatory cytokine level,protect organs from damage and confer a distinct survival advantage to the infected sepsis mice,demonstrating a promising agent for antioxidative therapy.4.AgNPs have been used as a broad-spectrum antimicrobial agent,whose toxicity originates from the localized release of Ag+ions.However,the residual AgNPs core would generate potential risk to humans and waste of noble metals.Herein,we infused the cysteine modified molybdenum disulfide with minimum Ag+ions and coated with a layer of cationic polyelectrolyte to construct an efficient and benign antimicrobial depot.The system exhibited much enhanced broad-spectrum antibacterial activity comparing with an equivalent amount of silver nitrate,owing to its increasing accessibility of released Ag+to the cell walls of microorganisms.More importantly,the antibacterial system could be successfully applied to treat wound infection,while retaining high antibacterial activities,exhibiting negligible biotoxicity and avoiding the waste of Ag.