Quaternary ammonium salt-based cross-linked micelle templated synthesis of highly active silver nanocomposite for synergistic anti-biofilm application

Abstract Persistent bacterial infection caused by biofilms is one of the most serious problems that endanger human health. Silver nanoparticles (AgNPs) are excellent candidates for removing bacterial biofilms, due to the inherent antimicrobial properties of silver with an increased surface-area ratio at the nanoscale. However, the stabilizers usually used on the surface of NPs to increase stability can block the activity of AgNPs and weaken their antimicrobial effects. Herein, a new quaternary ammonium salt-based cross-linked micelle (QAS@CM) templated synthesis of highly active silver nanocomposite (Ag@QAS@CM) was created for synergistic anti-biofilm effects. Ag@QAS@CM responded to the biofilm acidic microenvironment to release the naked AgNPs which would show better antibacterial activity because of the higher exposure of the surface area than that of the commercial PVP protected AgNPs (P-AgNPs). Enzyme activity experiments based on glucose oxidase (GOx) showed that the naked AgNPs in Ag@QAS@CM had higher activity (1.4 times) than P-AgNPs. Meanwhile, the QAS fragments released during micelle degradation, could synergistically eliminate biofilm with the naked AgNPs and reduce the dosage of AgNPs needed. Crystal violet (CV) assays, scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM) images revealed that the cooperative effect of the naked AgNPs and QAS fragments reduced the dosage of single-used AgNPs by 4 times and single-used QAS fragments by 2 times respectively. Moreover, blood compatibility and cytotoxicity assays showed that the nanocomposite exhibited biocompatibility with lower hemolysis rate and reduced cytotoxicity compared to P-AgNPs. Overall, our silver-based nanocomposite Ag@QAS@CM holds great potential in replacement of traditional antibiotics to treat persistent infection caused by biofilms.