Nanocatalysts promote Streptococcus mutans biofilm matrix degradation and enhance bacterial killing to suppress dental caries in vivo.
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.
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. Electronic address: lzgao@yzu.edu.cn.
Lizeng
L
Gao
Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yuan
Y
Liu
Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dongyeop
D
Kim
Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yong
Y
Li
Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Geelsu
G
Hwang
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Pratap C
PC
Naha
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
David P
DP
Cormode
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. Electronic address: koohy@dental.upenn.edu.
Hyun
H
Koo
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002384:Catalysis; D002460:Cell Line; D003731:Dental Caries / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D052203:Ferrosoferric Oxide / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009195:Peroxidase / Q000737:chemistry / Q000494:pharmacology; D013295:Streptococcus mutans / Q000187:drug effects* / Q000502:physiology
D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D006861:Hydrogen Peroxide; D009195:Peroxidase; D052203:Ferrosoferric Oxide
Antibacterial; Biofilms; Catalysis; Dental caries; Extracellular matrix; Iron oxide; Nanoparticles