Polymeric micellar nanoplatforms for Fenton reaction as a new class of antibacterial agents
Polymeric micellar nanoplatforms for Fenton reaction as a new class of antibacterial agents
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DOI：
10.1016/j.jconrel.2015.11.027
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发表时间：
2016-01-10
影响因子：
10.8
通讯作者：
Lee, Dongwon
中科院分区：
文献类型：
--
作者：
Park, Seong-Cheol;Kim, Nam-Hong;Lee, Dongwon
由宿主吞噬细胞产生的活性氧（ROS）对多种病原体发挥抗菌作用，ROS诱导的氧化应激是主要杀菌抗生素抗菌活性的控制机制。羟基自由基是一种强的非选择性氧化剂，可损伤DNA、蛋白质和脂质等生物分子。已知亚铁离子将温和的氧化剂过氧化氢（H2O2）转化为高反应性和毒性的羟基自由基，称为芬顿反应。在此，我们报告了一类新的抗菌剂的基础上芬顿反应执行的纳米结构，组成的过氧化氢生成聚合物（PCAE）和含铁的二茂铁。两亲性PCAE的目的是将H2O2产生肉桂醛通过酸可裂解的链接和自组装的formemandically稳定的胶束，可以封装在其疏水核心的二茂铁。所有体外实验均表明，二茂铁负载的PCAE胶束通过破坏细胞膜，产生羟自由基杀灭大肠杆菌和铜绿假单胞菌。腹腔注射二茂铁载药的胶束可显著减轻耐药铜绿假单胞菌感染小鼠的肺损伤，从而提高小鼠的存活率。鉴于其有效的抗菌活性，二茂铁负载的PCAE胶束作为一类新的ROS操纵抗菌剂具有很大的潜力。(C)2015 Elsevier B.V.版权所有。
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 formthermodynamically 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. (C) 2015 Elsevier B.V. All rights reserved.