Fabrication Of Yolk-Shell Nanocarrier Plateform And Study On Antimicrobial Biofilms

Eighty percent bacterial infection of human beings is relevant to bacterial biofilm.Biofilm infection has become one of the killers that threaten human life.Bacterial biofilm is a special matrix of the bacetria and the extracellular polymeric substances（EPS）secreted by the bacteria.Unlike free bacteria,bacteria in biofilms are surrounded by an abundance of EPS matrix,making it difficult for the antibacterial agents to kill the bacteria from outside to inside.Moreover,the bacteria and the EPS have different sensitivities to antibacterial agents,that is,the EPS has weak affinity with antibacterial agents while lipopolysaccharide and teichoic acid on the cell membrane（or cell wall）of the bacteria are highly sensitive to antibacterial agents.The heterogeneity in biofilm arsising from its component and stracture requires the antibacterial agents to be versatile,which a major challenge in clinical biofilm therapies.Consequently,developing anti-biofilm materials with high permeability to overcome the heterogeneity of biofilm becomes a challenge in order to suppress biofilm infection.This study developed a therapeutic strategy based on spatiotemporal controlled release to overcome biofilm heterogeneity.First,NONOate/NP@GA-Fe MOF nanomaterials with Yolk-Shell structure were prepared via two step emulsification followd by high pressure synthesis.The shell was GA-Fe MOF and the Yolk was NONOate/NP.Fe³⁺was loaded onto the shell of the nanomaterial,and the antimicrobial agent（NO）was loaded to the core of the nanomaterial as a result of high pressure synthesis.In the acidic microenvironment of biofilm,Fe³⁺in the shell of the nanomaterial was released,which generated ROS by Fenton reaction to significantly damage the EPS matrix.The NO in the Yolk was released through the magnetothermal effect.The NO penetrated the biofilm and reached the bacterial surface.This strategy utilized the pharmacokinetic complementarity of ROS and NO.ROS had short diffusion distance and strong oxidation without selection,and easily contacted and destroied EPS.This promoted the dispersion of NO with long diffusion distance and broad antibacterial spectrum into the biofilm and thus the elimination of internal bacteria.On the one hand,the effective bactericidal effect of the method was verified by in vitro experiments.On the other hand,in vivo experiments using three-dimensional spherical biofilms have also achieved good therapeutic effects,which demonstrates the high feasibility of the treatment concept of ROS-NO orderly controlled release.From an extended perspective,different antibacterial substances are loaded with Yolk-Shell nanomaterials,and orderly controlled release is achieved by cleverly designing the material structure,which synergistically improves the anti-biofilm effect.