FABRICATION OF N-HALAMINE NANOPARTICLES FOR ANTIMICROBIAL AND ANTIFOULING APPLICATIONS

Biofilm formation is a serious problem in the medical and industrial settings due to the increased resistance of these communities to killing compared to free-living bacteria. In addition, antimicrobial resistance is on the rise. This has prompted the search for agents that can inhibit both bacterial growth and withstand harsh conditions (e.g., high organic loads). In the current study, N-halamine-derivatized cross-linked polymethacrylamide nanoparticles (NPs) were synthesized by co-polymerization of the monomer methacrylamide (MAA) and the cross-linker monomer N,N-methylenebisacrylamide (MBAA), and were subsequently loaded with oxidative chlorine, using sodium hypochlorite (NaOCl). The chlorinated NPs demonstrated remarkable stability and durability to organic reagents and to repetitive bacterial loading cycles as compared with the common disinfectant NaOCl (bleach), which was extremely labile under these conditions. The antibacterial mechanism of the cross-linked P(MAA-MBAA)-Cl NPs was found to involve generation of reactive oxygen species (ROS) only upon exposure to organic media. Importantly, ROS were not generated upon suspension in water, revealing that the mode of action is target-specific. Further, a unique and specific interaction of the chlorinated NPs with Staphylococcus aureus was discovered, whereby these microorganisms were all specifically targeted and marked for destruction. This bacterial encircling that did not accrue with human cells was achieved without using a targeting module (e.g., an antibody or a ligand) and represents a highly beneficial, natural property of the P(MAA-MBAA)-Cl nano-structures. Finally, as a proof-of-concept of our technology, P(MAA-MBAA)-Cl NPs embedded within irrigation drippers were shown to prevent fouling on them compared with the control, hence providing the drippers with `self-cleaning` and `self-sterilizing` properties. In summary, our findings underscore the potential of developing sustainable P(MAA-MBAA)-Cl NPs-based devices for inhibiting bacterial colonization and growth.