Construction Of Mesoporous Silica Nanoparticle-Based Biohybrid Nanomaterials And Polyetherimide Derivatives For Antibacterial Application

Although antibiotics have been widely used in clinical applications to treat pathogenic infections at present,the problem of drug-resistance associated with abuse of antibiotics is becoming a potential threat to human beings.The increasing use of antibiotics leads to less favorable outcomes for society,and is harmful for the health.We report a biohybrid nanomaterial consisting of antibiotics,enzyme,polymers,hyaluronic acid(HA),and mesoporous silica nanoparticles(MSNs),which exhibits efficient in vitro and in vivo antibacterial activity with low cytotoxicity and negligible hemolytic side effect.Herein,biocompatible layer-by-layer(LBL)coated MSNs are designed and crafted to release encapsulated antibiotics,e.g.,amoxicillin(AMO),upon triggering with hyaluronidase,a factor of pathogenicity and invasion for bacteria like Staphylococcus aureus(S.aureus)and Escherichia coli(E.coli).The LBL coating process comprises lysozyme(Lys),HA and 1,2-ethanediamine(EDA)modified polyglycerol methacrylate(PGMA).The Lys and cationic polymers provided multivalent interactions between MSN-Lys-HA-PGMA and bacterial membrane and accordingly immobilized the nanoparticles to facilitate the synergistic effect of these antibacterial agents.Loading process was characterized by dynamic light scattering(DLS),transmission electron microscopy(TEM),thermo-gravimetric analysis(TGA),and Xray diffraction spectroscopy(XRD).The minimal inhibition concentration(MIC)of MSN-LysHA-PGMA treated to antibiotic resistant bacteria is much lower than that of isodose Lys and AMO.Especially,MSN-Lys-HA-PGMA exhibited good inhibition for pathogens in bacteriainfected wounds in vivo.Therefore,this type of new biohybrid nanomaterials will open up a new way for the design of next-generation of antibacterial agents as alternatives to antibiotics.Study on microorganisms has attracted increasing interest since the last several decades because of their significant roles in the areas ranging from environmental monitoring,medical hygiene,and food processing to pharmaceutical industry.The ability of bacteria is most commonly determined by plate count method,high-resolution microscopy and bacteriological detection and so on.However,these methods require expensive instrumentation and nontrivial preparation,while only applicable to limited targets,restricting their application in high throughput screenings.Fluorescence-based methods enjoy advantages such as high sensitivity,easy operation,and rapid response over other methods.Thus,we developed to a new plantform to combined polyethyleneimine derivatives with an aggregation-induced emission(AIE)molecules,TPE-DB,which can differentiate dead and living bacteria and serve as a highly fluorescent and photostable probe for long-term viability assay.Upon contacting with bacteria,the formation of PEI-CD-Arg/TPE-DB enhanced the flourencet intensity,exhibiting weakened flourencet intensity when the bacteria died.The coumpond possess dual functions of fluorometric detection and inhibition for bacteria in aqueous media.