Construction And Bactericidal Application Of Reactive Porphyrin-Based Covalent Organic Frameworks

Bacteria have super adaptability and reproduction rate,which can colonize wounds and cause serious infections,is a major health threat in the world.Although the emergence of antibiotics has effectively reduced the mortality rate of bacterial infections,it has also led to the emergence of drug-resistant bacteria.Phototherapy,including photothermal therapy and photodynamic therapy,has great application prospects in the treatment of bacterial infections due to its advantages such as broad-spectrum antibacterial activity,no drug resistance and simple operation.However,most of the current photosensitizers lack the ability to target bacteria,which can easily cause nonspecific damage to normal tissues.In addition,photosensitizers are prone to aggregate self quenching in the physiological environment and produce singlet oxygen（¹O₂）with a relatively short half life,leading to poor therapeutic effects.Due to its ordered structure,pore size,and ease of functionalization,covalent organic framework can well solve the shortcomings of traditional photosensitizers.Therefore,this paper designed and constructed an acrylate functionalized porphyrin covalent organic framework（TM）for reactive targeted photothermal/photodynamic/chemical sterilization.The main research contents are as follows:A photothermal/photodynamic/chemical bactericidal TM which can react with bacterial adhesion protein was constructed.TM was synthesized by hydrothermal method using photosensitizer aminoporphyrin as a ligand providing photothermal and photodynamic capabilities,and p-phthalaldehyde containing acrylate side chains as a ligand providing targeting capabilities for bacterial adhesins.Through the measurement of photodynamic and photothermal properties,it was found that the ordered crystal structure of TM can effectively avoid the self aggregation quenching of porphyrin monomers,facilitate the entry of oxygen and the transport of ¹O₂,and effectively increase the stacking density of porphyrins,exhibiting excellent optical properties.The reaction of TM with adhesin protein analogues indicates that the highly active double bonds in TM can react with sulfhydryl groups at room temperature,providing a guarantee for bacterial targeting.In addition,TM has structural and property stability in simulated physiological environments,laying the foundation for subsequent sterilization of wound infections.The bacterial killing ability of TM was studied.The results of plate coating,laser confocal microscopy,and scanning electron microscopy show that TM has a certain chemical bactericidal ability in the dark,which can reduce the survival rate of Escherichia coli and Staphylococcus aureus by more than 10%.Under the irradiation of a white LED lamp(100 m W cm^-2,30 min),the survival rate of the two bacteria is almost zero,and TM can adhere to the surface of the bacteria,immobilize the bacteria,and make the bacteria lose their colonization and diffusion ability.The dyeing results of DCFH-DA indicator showed that the bactericidal effect of TM was related to the production of ¹O₂.The above results provide a possibility for TM to be used for combined photothermal/photodynamic/chemical sterilization of bacterial infections.The combination of photothermal/photodynamic/chemical sterilization for bacterial infected wounds in mice has been achieved.TMG hydrogel was prepared by mixing TM with gelatin and sodium alginate.Through the plate coating experiment,it was found that TMG hydrogel had the same bactericidal ability as TM,which provided a guarantee for its use in the treatment of infected wounds on the back of mice.With the aid of light,TMG hydrogel has a good therapeutic effect on Staphylococcus aureus infected wounds,which can accelerate wound healing,reduce inflammatory reaction,and no obvious weight change and organ necrosis are found after treatment,which broadens the biological application of covalent organic framework materials and provides a new strategy for the design of new bactericidal materials.