Background:
Dental caries is the most prevalent bacterial biofilm-induced disease. Current clinical prevention and treatment agents often suffer from adverse effects on oral microbiota diversity and normal tissues, predominately arising from the poor biofilm-targeting property of the agents.
Methods:
To address this concern, we herein report dual-sensitive antibacterial peptide nanoparticles pHly-1 NPs upon acid and lipid-binding for treatment of dental caries. Amino acid substitutions were performed to design the peptide pHly-1. The potential, morphology and secondary structure of pHly-1 were characterized to elucidate the mechanisms of its pH and lipid sensitivity. Bacterial membrane integrity assay and RNA-seq were applied to uncover the antimicrobial mechanism of peptides under acidic condition. The
in vitro
and
ex vivo
antibiofilm assays were used to determine the antibiofilm performance of pHly-1 NPs. We also carried out the
in vivo
anti-caries treatment by pHly-1 NPs on dental caries animal model. Oral microbiome and histopathological analyses were performed to assess the
in vivo
safety of pHly-1 NPs.
Results:
The pHly-1 peptide underwent the coil-helix conformational transition upon binding to bacterial membranes in the acidic cariogenic biofilm microenvironment, thereby killing cariogenic bacteria. Under normal physiological conditions, pHly-1 adopted a
β
-sheet conformation and formed nanofibers, resulting in negligible cytotoxicity towards oral microbes. However, in acidic solution, pHly-1 NPs displayed reliable antibacterial activity against
Streptococcus mutans
, including standard and clinically isolated strains, mainly via cell membrane disruption, and also suppressed
in vitro
and human-derived
ex vivo
biofilm development. Compared to the clinical agent chlorhexidine,
in vivo
topical treatment with pHly-1 NPs showed an advanced effect on inhibiting rat dental caries development without adverse effects on oral microbiota diversity and normal oral or gastric tissues.
Conclusion:
Our results demonstrated the high efficacy of dual-sensitive antimicrobial peptides for the selective damage of bacterial biofilms, providing an efficient strategy for preventing and treating dental caries.
Based on geological studies, 141 rock analyses and 5 trace element analyses of metabasites, the present paper deals with the rock association, chemical features, protolith formation and the original tectonic settings upwards through the Lower Proterozoic metamorphic strata in the Dabieshan-Lianyungang area, in the south-east of the North China Platform. The results of the study indicate that the lower and middle parts of the metamorphic strata comprise terrigenous clastics, phosphoritic and aluminous sedimentary formations which formed under stable continental margin conditions. In the middle-upper part a calc-alkaline volcano-sedimentary formation under the active continental margin was developed. The Lower Proterozoic meta-strata of sedimentary-volcanosedimentary origin from bottom upwards suggest that the tectonic evolution of the south-eastern margin of the North China Platform is a process from stabilization to mobilization. This process suggests a northward subduction of the Yangtze Plate under the North China Plate during the later part of the early Proterozoic.
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