title: Polymeric micellar nanoplatforms for Fenton reaction as a new class of antibacterial agents.
abstract: Reactive oxygen species (ROS) produced by host phagocytes exert antibacterial action against a variety of pathogens and ROS-induced oxidative stress is the governing mechanism for the antibacterial activity of major bactericidal antibiotics. In particular, hydroxyl radical is a strong and nonselective oxidant which can damage biomolecules such as DNA, proteins and lipids. Ferrous ion is known to convert mild oxidant hydrogen peroxide (H2O2) into highly reactive and toxic hydroxyl radicals, referred to as Fenton reaction. Herein, we report a new class of antibacterial agents based on Fenton reaction-performing nanostructures, composed of H2O2-generating polymer (PCAE) and iron-containing ferrocene. Amphiphilic PCAE was designed to incorporate H2O2-generating cinnamaldehyde through acid-cleavable linkages and self-assemble to form thermodynamically stable micelles which could encapsulate ferrocene in their hydrophobic core. All the experiments in vitro display that ferrocene-loaded PCAE micelles produce hydroxyl radicals to kill Escherichia coli and Pseudomonas aeruginosa through membrane damages. Intraperitoneally injected ferrocene-loaded PCAE micelles significantly reduced the lung damages and therefore increased the survival rate of mice infected with drug resistant P. aeruginosa. Given their potent antibacterial activity, ferrocene-loaded PCAE micelles hold great potential as a new class of ROS-manipulating antibacterial agents.
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Chonnam, 540-950, Republic of Korea.
authors.forename: Seong-Cheol
authors.initials: SC
authors.lastname: Park
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Chonnam, 540-950, Republic of Korea.
authors.forename: Nam-Hong
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Department of BIN Convergence Technology, 567 Baekje-daero, Chonbuk National University, Jeonju, Chonbuk 561-756, Republic of Korea.
authors.forename: Wonseok
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Chonnam, 540-950, Republic of Korea.
authors.forename: Jae-Woon
authors.initials: JW
authors.lastname: Nah
authors.affiliation: Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Chonnam, 540-950, Republic of Korea.
authors.forename: Mi-Kyeong
authors.initials: MK
authors.lastname: Jang
authors.affiliation: Department of BIN Convergence Technology, 567 Baekje-daero, Chonbuk National University, Jeonju, Chonbuk 561-756, Republic of Korea; Department of Polymer⋅Nano Science and Technology, 567 Baekje-daero, Chonbuk National University, Jeonju, Chonbuk 561-756, Republic of Korea. Electronic address: dlee@chonbuk.ac.kr.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D000075163:Metallocenes; D051379:Mice; D008813:Mice, Inbred ICR; D008823:Micelles; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C045076:Fenton's reagent; D005296:Ferrous Compounds; D000075163:Metallocenes; D008823:Micelles; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D000171:Acrolein; D006861:Hydrogen Peroxide; D007501:Iron; C012843:cinnamaldehyde; C004998:ferrocene
keywords: Antibacterial; Fenton reaction; Hydroxyl radical; Micelles; Polymers