Stimuli-responsive, antimicrobial-loaded nanocarriers for oral biofilm control and microbiome restoration

Abstract

Nanotechnology has provided thousands of novel nano-antimicrobials possessing features uncommon in clinically available antimicrobials. Here, nanocarriers loaded with conventional antimicrobials and responding to environmental changes upon entry into oral biofilms are reviewed. Supra-gingival biofilms are characterized by acidic pH, the presence of bacterial enzymes, and the development of hypoxia in deeper layers. Sub-gingival biofilms are slightly alkaline, with hypoxia occurring over their entire depth. Upon entering biofilms, negatively charged, pH- and/or hypoxia-responsive nanocarriers become positively charged. This charge reversal leads to electrostatic double-layer attraction between positively charged nanocarriers towards negatively charged, water-filled channel walls in biofilms, enhancing their accumulation in a biofilm. Degradation of bacterial enzyme-responsive nanocarriers causes in-biofilm release of antimicrobial cargo, yielding higher local antimicrobial concentrations than can be achieved through their direct, oral administration without harming soft tissues. Enhanced antibiofilm activity after in-biofilm antimicrobial release from biofilm-responsive micelles and liposomes has been demonstrated in vitro towards single-species Streptococcus mutans and Staphylococcus aureus biofilms or in vivo using specific-pathogen-free rodents inoculated with selected pathogens. This preferential antibacterial activity regulated the microbial composition of ex vivo human oral biofilm towards a more healthy microbiome composition. Although clinical confirmation is limited, the potential benefits of stimuli-responsive, antimicrobial-loaded nanocarriers for oral biofilm control and microbiome restoration are worth further investigation towards clinical translation.

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Funding

This work was supported by the National Science Fund for Excellent Young Scholars (32322044), the CQMU Program for Youth Innovation in Future Medicine (W0077), the Program for Scientific and Technological Innovation Leader of Chongqing (CQYC20220303655).

This work was supported by the Young Scientists Fund of the National Natural Science Foundation of China (82301144).

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