Precision targeting of bacterial pathogen via bi-functional nanozyme activated by biofilm microenvironment

Human dental caries is an intractable biofilm-associated disease caused by microbial interactions and dietary sugars on the host's teeth. Commensal bacteria help control opportunistic pathogens via bioactive products such as hydrogen peroxide (H2O2). However, high-sugar consumption disrupts hom...

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Bibliographic Details
Published in:Biomaterials 2021-01, Vol.268, p.120581-120581, Article 120581
Main Authors: Huang, Yue, Liu, Yuan, Shah, Shrey, Kim, Dongyeop, Simon-Soro, Aurea, Ito, Tatsuro, Hajfathalian, Maryam, Li, Yong, Hsu, Jessica C., Nieves, Lenitza M., Alawi, Faizan, Naha, Pratap C., Cormode, David P., Koo, Hyun
Format: Article
Language:English
Subjects:
Biofilm
Biofilms
Catalytic nanoparticles
Dental caries
Dental Caries - drug therapy
Glucose oxidase
Humans
Hybrid nanozyme
Hydrogen Peroxide
Microbial Interactions
Polymicrobial
Streptococcus mutans
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Summary:Human dental caries is an intractable biofilm-associated disease caused by microbial interactions and dietary sugars on the host's teeth. Commensal bacteria help control opportunistic pathogens via bioactive products such as hydrogen peroxide (H2O2). However, high-sugar consumption disrupts homeostasis and promotes pathogen accumulation in acidic biofilms that cause tooth-decay. Here, we exploit the pathological (sugar-rich/acidic) conditions using a nanohybrid system to increase intrinsic H2O2 production and trigger pH-dependent reactive oxygen species (ROS) generation for efficient biofilm virulence targeting. The nanohybrid contains glucose-oxidase that catalyzes glucose present in biofilms to increase intrinsic H2O2, which is converted by iron oxide nanoparticles with peroxidase-like activity into ROS in acidic pH. Notably, it selectively kills Streptococcus mutans (pathogen) without affecting Streptococcus oralis (commensal) via preferential pathogen-binding and in situ ROS generation. Furthermore, nanohybrid treatments potently reduced dental caries in a rodent model. Compared to chlorhexidine (positive-control), which disrupted oral microbiota diversity, the nanohybrid had significant higher efficacy without affecting soft-tissues and the oral-gastrointestinal microbiomes, while modulating dental health-associated microbial activity in vivo. The data reveal therapeutic precision of a bi-functional hybrid nanozyme against a biofilm-related disease in a controlled-manner activated by pathological conditions. [Display omitted]
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2020.120581