Gao Lizeng, Liu Yuan, Kim Dongyeop, Li Yong, Hwang Geelsu, Naha Pratap C, Cormode David P, Koo Hyun
Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Orthodontics and Divisions of Pediatric Dentistry & Community Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Biomaterials. 2016 Sep;101:272-84. doi: 10.1016/j.biomaterials.2016.05.051. Epub 2016 Jun 2.
Dental biofilms (known as plaque) are notoriously difficult to remove or treat because the bacteria can be enmeshed in a protective extracellular matrix. It can also create highly acidic microenvironments that cause acid-dissolution of enamel-apatite on teeth, leading to the onset of dental caries. Current antimicrobial agents are incapable of disrupting the matrix and thereby fail to efficiently kill the microbes within plaque-biofilms. Here, we report a novel strategy to control plaque-biofilms using catalytic nanoparticles (CAT-NP) with peroxidase-like activity that trigger extracellular matrix degradation and cause bacterial death within acidic niches of caries-causing biofilm. CAT-NP containing biocompatible Fe3O4 were developed to catalyze H2O2 to generate free-radicals in situ that simultaneously degrade the biofilm matrix and rapidly kill the embedded bacteria with exceptional efficacy (>5-log reduction of cell-viability). Moreover, it displays an additional property of reducing apatite demineralization in acidic conditions. Using 1-min topical daily treatments akin to a clinical situation, we demonstrate that CAT-NP in combination with H2O2 effectively suppress the onset and severity of dental caries while sparing normal tissues in vivo. Our results reveal the potential to exploit nanocatalysts with enzyme-like activity as a potent alternative approach for treatment of a prevalent biofilm-associated oral disease.
牙菌斑生物膜(即牙菌斑)极难清除或治疗,因为细菌会被困在保护性的细胞外基质中。它还会形成高度酸性的微环境,导致牙齿上的釉质磷灰石发生酸溶解,从而引发龋齿。目前的抗菌剂无法破坏这种基质,因此无法有效杀死牙菌斑生物膜内的微生物。在此,我们报告了一种控制牙菌斑生物膜的新策略,即使用具有过氧化物酶样活性的催化纳米颗粒(CAT-NP),它能引发细胞外基质降解,并在致龋生物膜的酸性微环境中导致细菌死亡。含有生物相容性Fe3O4的CAT-NP被开发出来,以催化H2O2原位生成自由基,同时降解生物膜基质,并以极高的效率(细胞活力降低>5个对数)迅速杀死嵌入其中的细菌。此外,它还具有在酸性条件下减少磷灰石脱矿的额外特性。通过类似于临床情况的每日1分钟局部治疗,我们证明CAT-NP与H2O2联合使用能有效抑制龋齿的发生和严重程度,同时在体内保护正常组织。我们的结果揭示了利用具有酶样活性的纳米催化剂作为治疗一种常见的生物膜相关口腔疾病的有效替代方法的潜力。