Structure-property correlations of reactive oxygen species-responsive and hydrogen peroxide-eliminating materials with anti-oxidant and anti-inflammatory activities
Structure-property correlations of reactive oxygen species-responsive and hydrogen peroxide-eliminating materials with anti-oxidant and anti-inflammatory activities
复制标题
活性氧响应和过氧化氢消除材料与抗氧化和抗炎活性的结构-性质相关性
DOI：
10.1021/acs.chemmater.7b02412
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发表时间：
2017
影响因子：
8.6
通讯作者：
Zhang Jianxiang
中科院分区：
文献类型：
--
作者：
Zhang Qixiong;Zhang Fuzhong;Chen Yue;Dou Yin;Tao Hui;Zhang Dinglin;Wang Ruibing;Li Xiaohui;Zhang Jianxiang
为了开发活性氧（ROS）响应性抗炎材料并建立其结构与性能的相关性，设计并合成了一系列清除H2 O2的材料（OxbCD）。这两个H2 O2引发的水解配置文件和H2 O2消除这些材料的能力是依赖于PBAP部分的化学结构。结合水解机制的阐明，我们建立了这些OxbCD材料的结构-性质相关性。广泛的体外实验表明，基于OxbCD的纳米颗粒（NPs）对正常细胞没有不良生物学效应。OxbCD NPs能有效抑制巨噬细胞的炎症反应和氧化应激。一致地，OxbCD NP有效地减轻小鼠腹膜炎的症状，关于减少中性粒细胞和巨噬细胞的计数以及抑制促炎细胞因子、趋化因子和氧化介质的分泌。类似地，负载有抗炎药物的OxbCD NP在小鼠腹膜炎的急性炎症模型中显示出上级功效。更重要的是，OxbCD NPs在通过不同途径给药后显示出良好的生物相容性。因此，除了作为抗炎材料外，新开发的H2 O2-消除材料可以用作与炎症和氧化应激相关的许多疾病的靶向治疗的功能性载体。
To develop reactive oxygen species (ROS)-responsive anti-inflammatory materials and establish their structure–property correlations, a series of H2O2-eliminating materials (OxbCDs) were designed and synthesized by conjugating different phenylboronic acid pinacol ester (PBAP) groups onto a biocompatible scaffold compound β-cyclodextrin via varied linker groups. Both the H2O2-triggered hydrolysis profiles and H2O2-eliminating capacities of these materials were dependent on the chemical structure of the PBAP moieties. Together with the elucidation of hydrolysis mechanisms, we established structure–property correlations of these OxbCD materials. Extensive in vitro experiments revealed nanoparticles (NPs) based on OxbCDs showed no adverse biological effects on normal cells. OxbCD NPs could effectively inhibit inflammatory responses and oxidative stress in stimulated macrophages. Consistently, OxbCD NPs efficaciously alleviated the symptoms of peritonitis in mice, with respect to reducing the counts of neutrophils and macrophages as well as inhibiting the secretion of pro-inflammatory cytokines, chemokines, and oxidative mediators. Similarly, OxbCD NPs loaded with anti-inflammatory drugs displayed superior efficacy in an acute inflammation model of peritonitis in mice. More importantly, OxbCD NPs showed good biocompatibility after administration via different routes. Consequently, besides serving as anti-inflammatory materials, the newly developed H2O2-eliminating materials may be utilized as pharmacologically functional carriers for targeted therapy of many diseases associated with inflammation and oxidative stress.