Precision targeting of bacterial pathogen via bi-functional nanozyme activated by biofilm microenvironment. (January 2021)

• Record Type: Journal Article
• 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
• Is Part Of: Biomaterials. Volume 268(2021)
• Publication Date: 2021-01
• Subjects: Hybrid nanozyme -- Glucose oxidase -- Catalytic nanoparticles -- Biofilm -- Polymicrobial -- Dental caries; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2020.120581
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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 (H2 O2 ). 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 H2 O2 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 H2 O2, 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. Graphical abstract: Image 1