title: Nanoparticle (star polymer) delivery of nitric oxide effectively negates Pseudomonas aeruginosa biofilm formation.
abstract: Biofilms are increasingly recognized as playing a major role in human infectious diseases, as they can form on both living tissues and abiotic surfaces, with serious implications for applications that rely on prolonged exposure to the body such as implantable biomedical devices or catheters. Therefore, there is an urgent need to develop improved therapeutics to effectively eradicate unwanted biofilms. Recently, the biological signaling molecule nitric oxide (NO) was identified as a key regulator of dispersal events in biofilms. In this paper, we report a new class of core cross-linked star polymers designed to store and release nitric oxide, in a controlled way, for the dispersion of biofilms. First, core cross-linked star polymers were prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) via an arm first approach. Poly(oligoethylene methoxy acrylate) chains were synthesized by RAFT polymerization, and then chain extended in the presence of 2-vinyl-4,4-dimethyl-5-oxazolone monomer (VDM) with N,N-methylenebis(acrylamide) employed as a cross-linker to yield functional core cross-linked star polymers. Spermine was successfully attached to the star core by reaction with VDM. Finally, the secondary amine groups were reacted with NO gas to yield NO-core cross-linked star polymers. The core cross-linked star polymers were found to release NO in a controlled, slow delivery in bacterial cultures showing great efficacy in preventing both cell attachment and biofilm formation in Pseudomonas aeruginosa over time via a nontoxic mechanism, confining bacterial growth to the suspended liquid.
authors.affiliation: Australian Centre for Nanomedicine and ‡Centre for Advanced Macromolecular Design (CAMD), School of Chemical Engineering, §School of Chemistry, and ∥Centre for Marine Bio-Innovation, School of Biotechnology and Biomolecular Sciences, University of New South Wales , Sydney, New South Wales, Australia 2052.
authors.forename: Hien T T
authors.initials: HT
authors.lastname: Duong
authors.forename: Kenward
authors.initials: K
authors.lastname: Jung
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Kutty
authors.forename: Sri
authors.initials: S
authors.lastname: Agustina
authors.forename: Nik Nik M
authors.initials: NN
authors.lastname: Adnan
authors.forename: Johan S
authors.initials: JS
authors.lastname: Basuki
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Barraud
authors.forename: Cyrille
authors.initials: C
authors.lastname: Boyer
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D009569:Nitric Oxide / Q000737:chemistry* / Q000494:pharmacology; D011095:Polyethylenes / Q000737:chemistry; D058105:Polymerization; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008689:Methacrylates; D011095:Polyethylenes; D009569:Nitric Oxide