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四氧化三铁纳米酶清除口腔细菌生物膜和预防龋齿的效果与机理
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摘要
生物膜感染难以治疗的主要原因之一是常用的抗菌剂很难突破基质屏障杀灭内部细菌,造成临床效果不佳。比如致龋性口腔生物膜[1],在牙齿表面形成后难以清除,其内变异链球菌难以杀灭并产酸,造成牙齿表面钙溶解脱矿,最终诱发龋齿等疾病,在儿童和成人中均具有很高的患病率,严重影响人们的健康和生活。为此,我们提出利用四氧化三铁纳米酶介导的过氧化物催化反应[2]降解生物膜基质屏障和杀灭内部细菌[3],实现口腔生物膜的高效清除。以变异链球菌生物膜模型为对象并模拟临床处理方法,我们发现四氧化三铁纳米酶可以巧妙利用口腔致龋性生物膜内的酸性环境,有效降解生物膜基质中的多糖和快速杀灭内部细菌(杀菌数量多达5个log)。此外四氧化三铁还具有防止牙齿脱矿的作用,动物实验显示四氧化三铁纳米酶可以有效预防龋齿并具有较好的生物安全性。该研究工作表明纳米酶在生物膜清除和龋齿防治中具有多种生物效应[4],为口腔生物膜清除和龋齿预防提供了新的策略,同时也为其他生物膜相关疾病的治疗提供参考。
Biofilm-associated infections are notoriously difficult to treat because the bacteria are enmeshed in a protective extracellular matrix and antimicrobial drugs cannot break through the matrix and kill the internal microbes. Here, we report a novel strategy to control oral disease-causing biofilms using Fe_3O_4 nanozymes with peroxidase-like activity that disrupt extracellular matrix and kill bacteria within acidic niches of cariogenic biofilm. Fe_3O_4 nanozymes were developed to degrade the biofilm matrix and kill the embedded bacteria with exceptional efficacy(>5-log reduction of cell viability) within 5 minutes. Moreover, it displays a unique property of reducing apatite demineralization in acidic conditions. Using a 1-minute topical daily treatment akin to a clinical situation, we demonstrate that Fe_3O_4 nanozymes effectively suppress the onset and severity of caries while sparing normal tissues in vivo. Our results reveal the potential to exploit nanozymes for the treatment of biofilm-associated oral disease.
引文
[1]Hwang G,Marsh G,Gao L,et al.Journal of dental research,2015,94:1310.
    [2]Gao L,Zhuang J,Nie L,et al.Nature nanotechnology,2007,2:577.
    [3]Gao L,Giglio KM,Nelson JL,et al.Nanoscale,2014,6:2588.
    [4]Gao L,Yan X.Science China Life sciences,2016,[Epub ahead of print].

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