Enzyme-like Properties Of Copper-based Nanomaterials And Their Antibacterial And Diabetic Chronic Wound Treatment Applications

Nanozymes,nanomaterials with enzyme-like activities,are becoming powerful competitors and potential substitutes for natural enzymes because of their excellent performance,such as tunable catalytic activity,high stability against harsh conditions,flexibility in composition and structural design,and excellent biocompatibility.In recent years,various nanozymes have been discovered or designed,and gradually applied in fields such as biosensing,therapeutics,and environmental protection.Although significant progresses have been made,there are some issues that still remain in the development of nanozymes,such as limited types,most are oxidoreductases;low antibacterial properties and often require the auxiliary conditions;less researches on inflammatory diseases.In this thesis,the enzyme-like properties of copper-based nanomaterials and their antibacterial and diabetic chronic wound treatment applications were systematically studied based on the research status of nanozymes.The main contents are as follows:1.Transition metal phosphides（TMPs）are important catalysts for quite a few of general catalytic reactions while their potentials for biological catalysis were seldom explored.Herein,we investigated the enzyme-like properties of four TMPs（FeP、CoP、Ni₂P,and Cu₃P）.We found that Cu₃P nanoparticles（NPs）were capable to efficiently catalyze the hydrolysis of glycosidic bonds as glycoside hydrolase mimics.In addition,Fe P NPs possessed both glucose oxidase-like（GOx-like）and peroxidase-like（POD-like）activities,which combined into a cascade reaction for the colorimetric detection of glucose.2.In this work,we proposed that Cu₃P NPs are an efficient broad-spectrum antibacterial agent,which can achieve 99.9%inactivation for both sensitive and resistant strains(3×10⁶ CFU m L^-1),and the microbial populations from a fishery water at a low concentration(≤1.5μg m L^-1).The antibacterial mechanism of Cu₃P NPs relied on the synergistic effect of their own multiple enzyme-like activities.Compared with the conventional antibiotics,the delayed bacterial resistance onset for application of Cu₃P NPs was demonstrated by antibiotic resistance bacteria-inducing experiment.In addition,Cu₃P NPs showed no obvious toxicity at the antibacterial concentrations in use.This work advances the practical application of nanoantibacterial agents,and this strategy is applicable to the study of other antibacterial materials against bacterial resistance.3.Persistent and hyperactive inflammatory response in chronic wounds is its primary difference from normal wounds.Focusing on this characteristic,we presented a strategy for diabetic chronic wound healing MOF nanozyme-based antioxidative system（MOF/Gel）.By virtue of the superoxide dismutase-like（SOD-like）and catalase-like（CAT-like）activities of the MOF nanozymes,MOF/Gel can scavenge reactive oxygen species（ROS）to modulated oxidative stress microenvironment in diabetic chronic wounds.Diabetic chronic wound healing experiments indicated that the efficacy of MOF/Gel was comparable to that of Human Epidermal Growth Factor Gel（HEGFG）.In addition,MOF nanozymes exhibited good biosafety.The stable,safe,and convenient MOF/Gel can meet the complex clinical demands.