Acceleration of Nitric Oxide Release in Multilayer Nanofilms through Cu(II) Ion Intercalation for Antibacterial Applications

Implant-derived bacterial infection is a prevalent cause of diseases, and no antibacterial coating currently exists that is biocompatible and that does not induce multidrug resistance. To this end, nitric oxide (NO) has been emerging as an effective antimicrobial agent that acts on a broad range of bacteria and elicits no known resistance. Here, a method for accelerating NO release from multilayered nanofilms has been developed for facilitating antibacterial activity. A previously reported multilayered nanofilm (nbi film) was fabricated by alternative deposition of branched polyethyleneimine (BPEI) and alginate via the layer-by-layer assembly method. N-Diazeniumdiolate, a chemical NO donor, was synthesized at the secondary amine moiety of BPEI within the film (nbi/NO film). Cu(II) ions can be incorporated into the film by forming chelating compounds with unreacted amines that have not been converted to NO donors. The increase of the amine protonation state in the chelate caused destabilization of the NO donor by reducing hydrogen bonding between the deprotonated amine and the NO donor. Thus, the Cu(II) ion-embedding film presented accelerated NO release and was further subjected to antibacterial testing to demonstrate the correlation between the NO release rate and the antibacterial activity. This study aimed to establish a novel paradigm for NO-releasing material design based on multilayered nanofilms by presenting the correlation between the NO release rate and the antibacterial effect.