Research On The Treatment Of Infectious Biofilm By Micro-Nano Materials

So far,bacterial infection is still a serious medical problem.In the process of fighting against bacteria,along with the continuous improvement of medical level,the problem of bacterial resistance is also expanding.Some bacteria have evolved efflux drug system osmotic barrier inactivated enzymes and altered target mechanisms to evade conventional antibiotics.What’s more,biofilms are organized colonies of bacteria surrounded by a matrix of extracellular polymers（EPS）that are more resistant to antibiotics than planktonic bacteria.Therefore,the development of therapeutic measures to reduce biofilm formation has gradually become the focus of scientific and medical research.Initial studies have focused on additive methods,such as coating,but additive methods have become less attractive as we need a long-term antimicrobial strategy due to disadvantages such as sensitization to patient tissues,toxicity and increased antibiotic resistance.Nowadays,in order to inhibit the formation of biofilm,many different methods have been adopted.Compared with passive coating methods,it can only slow down the formation of biofilm,but it is difficult to completely eliminate the bacteria inside it.Therefore,the in-depth exploration of micro-nanomaterials in antibacterial and biofilm elimination can develop a better treatment of pathogenic microbial infection,and contribute to world health security.In addition,the current prevention and control methods of biofilms mainly include physical means（such as ultrasound,photothermal,magnetic force）chemical means（such as metal ions,amphiphilic cation molecules and surfactants）and biological means（such as antibiotics,antimicrobial peptides,enzymes,monoclonal antibodies and bacteriophages）.However,due to the continuous development of bacterial resistance,a single antibacterial mechanism often cannot completely eliminate bacteria,and biofilm tend to be highly tolerated,so that a single method becomes helpless.Usually,some researchers will use the physical and chemical properties of multiple materials to cross-link and modify each other,and the synergistic effect of multiple materials can produce ten or even one hundred or one thousand times of enhanced therapeutic effect.Therefore,we developed a novel approach to design a nano enzyme of GO based nitrotriacetate-cerium（IV）complex（GO-NTA-Ce）for the treatment of bacterial biofilm infection.Specifically,GO-NTA-Ce is an artificial enzyme with DNase-like activity,showing high shearing ability for both DNA model substrate（BNPP）and extracellular DNA（e DNA）.When located at bacteria-associated infection sites,GO-NTA-Ce inhibits biofilm formation and effectively disperses the formed biofilm by degrading e DNA.In addition to Ce-mediated DNase-like activity,near-infrared laser irradiation of GO-NTA-Ce produced local hyperheat killing of bacteria protected by biofilm matrix.Furthermore,graphene itself is a novel green broad-spectrum antibacterial material that can exert its antibacterial effects through physical damage（such as direct contact with bacterial membranes with its sharp edges and destructive extraction of lipid molecules）and chemical damage（reactive oxygen species production and charge transfer due to oxidative stress）.In short,our GO-NTA-Ce nano enzyme platform is able to effectively eliminate drug-resistant bacterial biofilm infections through a triple action of DNase-like enzyme properties,photothermal therapy and graphene-based antibacterial activity.In exploring the practical operation of treating infectious biofilms,we found that when biofilms were formed,the therapeutic effect of using GO-NTA-Ce nanomaterials alone was hindered due to its strong resistance barrier.To this end,we designed and constructed another novel method to remove infectious biofilms.Specifically,we propose a mesoporous silica microjet as an artificial carrier supported catalyst and magnetic nanoparticles drug delivery device.The system can remove mature biofilms only by physically striking and dispersing the refractory matrix and destroying the membrane structure and internal components of pathogens without developing drug resistance.Experiments have shown that once the S.aureus biofilm is exposed to a low concentration of H₂O₂,the FMM will perform high-speed ejection motion,and the magnetic force forces the FMM’s motion to target precisely,dispersing the solid biofilm matrix with physical blows.Our experiments show that FMM with peroxise-like activity can convert H₂O₂ to more cytotoxic·OH,and this system can effectively remove infectious biofilms using a simple and novel method.In conclusion,the two micro-nanomaterials we developed have unique insights in the exploration of infectious biofilms:not only avoiding the use of antibiotics,but also complementing the lack of a single antibacterial mechanism.They can effectively degrade stubborn biofilm matrix components and kill encapsulated bacteria,which is important for the design of resistance to multidrug-resistant bacterial biofilm infection systems.