Construction Of Metal-organic Framework Nanosystem With Enzymatic Catalytic Properties And Study On Antibacterial Mechanism

Pathogenic bacterial infection has not only become a serious threat to human health but also caused great damage to people’s property.Currently,antibiotics such as vancomycin are regarded as one of the major therapeutic strategies to combat bacterial infections.However,the abuse of antibiotics leads to the emergence of bacterial resistance,which greatly impairs the antibacterial effect of traditional antibiotics.Therefore,it is one of the significant challenges to seek novel strategies for global public health to efficiently eliminate bacteria without inducing drug resistance.Metal-organic frameworks（MOFs）with a variety of advantages such as diverse structures,high specific surface area,and excellent biocompatibility,show outstanding prospects in the field of antibacterial therapy.Recently,MOFs-based photodynamic therapy（PDT）and chemodynamic therapy（CDT）are typical approaches to killing bacteria by reactive oxygen species（ROS）without drug resistance.However,the light in PDT hardly reaches the deep tissue of bacterial infection tissue due to the unpromising penetrating power of specific light wavelengths.Notably,the ROS generation efficiency is highly dependent on oxygen（O₂）in the surrounding microenvironment,and the microenvironment of bacterial infection is hypoxic,which eminently limits the therapeutic effect of PDT.Additionally,the catalytic efficiency of nanozyme severely limits the CDT-mediated antibacterial therapy.To address these issues,we fabricate a self-light-emitting nanoreactor for PDT-induced antibacterial treatment and two-dimensional copper-based MOFs nanosheets（2D MOF NSs）with efficient peroxidase（POD）properties for CDT-mediated antibacterial therapy.Specifically,the works are presented as follows:1.Due to the limited penetration depth of light and O₂-dependent ROS generation capacity of PDT,an antimicrobial nanoreactor（PLMG）is reported,which is constructed by Luminol-loaded PCN-224,and further coated with manganese dioxide（Mn O₂）and adsorbing glucose oxidase（GOx）.It realizes the self-sufficiency of PDT light and efficient alleviation of the hypoxic condition in the bacterial infection location,which overcomes the drawback of the low tissue-penetrating depth of light and improves the ROS generation efficiency of PDT.GOx catalyzes glucose to generate more hydrogen peroxide（H₂O₂）,while Mn O₂catalyzes H₂O₂to produce more O₂.PCN-224photosensitizer reacts with O₂to generate ROS under the irradiation of light induced by the reaction of Luminol and H₂O₂,achieving the efficiently antibacterial performance of PDT.The experimental results demonstrate that in the presence of H₂O₂and glucose,PLMG（16μg/m L）exhibits a 99.98%bactericidal effect on S.aureus and a good elimination of biofilms.The hemolysis and cytotoxicity analysis show the good biocompatibility of PLMG.Therefore,we innovatively designed a self-luminescent nanomaterial with a superb antibacterial potential,which overcomes the poor penetration of external light in PDT.This work provides a new approach to the construction of a novel nano-antibacterial platform without the limitation of the external light with poor tissue-penetrating capacity and the hypoxic condition in the bacterial infection microenvironment.2.To avoid the damage caused by traditional therapy to normal tissues and the unideal bactericidal effect due to the low enzyme activity in CDT,2D Cu-MOF NSs,a nano-enzyme,were prepared via a simple one-step method.The nanosystem shows a POD activity,and the Cu⁺as activated sites can react with H₂O₂to produce highly toxic hydroxyl radical（·OH）to kill bacteria.Meanwhile,the 2D morphology of Cu-MOF NSs provides a high density of Cu²⁺/Cu⁺surface active site,which can induce damage to S.aureus by oxidizing proteins and lipids on bacterial surfaces.2D Cu-MOF NSs overcome the limitations of traditional therapeutic modalities that ROS production requires external stimulation,and avoid damage to normal tissues.The experimental results show that the antibacterial rate of Cu-MOF NSs at the concentration of 4μg/m L is up to 99.9%,and exhibit a tremendous eradication effect on S.aureus biofilm with high biosafety.