Metformin-loaded mesoporous calcium silicate nanoparticles against alkaline-resistant Enterococcus faecalis infection
- 1The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China
Abstract
Background Enterococcus faecalis (E. faecalis) contributes to persistent endodontic infections through biofilm formation, dentinal tubule invasion, and alkaline resistance, which limits the efficacy of calcium hydroxide. Metformin (Met) attenuates this resistance by interfering with bacterial metabolic adaptation. Combining Met with mesoporous calcium silicate nanoparticles (MCSNs), which possess intrinsic alkaline antibacterial activity and sustained drug-delivery capabilities, may enhance the elimination of alkaline-resistant E. faecalis and promote periapical healing.Methods Metformin-loaded MCSNs (MCSNs-Met) were characterized for physicochemical properties, Met release, alkalinity, cytocompatibility, and dentinal tubule penetration. Antibiofilm activity against highly alkaline-resistant E. faecalis was assessed using infected dentin models. Therapeutic efficacy was further evaluated in a beagle model of E. faecalis-induced apical periodontitis using Micro-CT and histological analyses.Results MCSNs-Met exhibited a uniform mesoporous structure, sustained Met release and alkalinity, favorable cytocompatibility, and enhanced dentinal tubule penetration. Compared with MCSNs alone, MCSNs-Met more effectively disrupted E. faecalis biofilms and reduced viable bacterial signals. In vivo, MCSNs-Met produced the greatest reduction in periapical bone resorption, markedly decreased residual bacterial signals and inflammatory infiltration, reduced osteoclast activity, and enhanced collagen deposition and periapical tissue repair.Conclusions MCSNs-Met integrates sustained Met delivery with the intrinsic alkaline and bioactive properties of calcium silicate nanoparticles, thereby enhancing control of highly alkaline-resistant E. faecalis and promoting periapical healing.
Related
- Functional genomic characterization of anti-phage defense systems in vancomycin-resistant Enterococcus faecium
- 4-phenylbutyric acid-loaded mesoporous silica nanoparticles alleviate endoplasmic reticulum stress and reduce intraocular pressure in glaucoma model
- Resolution of chromosomal structural variation and vanA plasmid dynamics by nanopore-only sequencing across successive waves of a hospital outbreak of vancomycin-resistant Enterococcus faecium
- Genomic insight into Enterococcus faecium biofilm formation isolated from catheter associated urinary tract infection
- Establishment of a reproducible Enterococcus cecorum infection model under farm conditions
BibTeX
@article{liu2026metforminloaded,
title = {{Metformin-loaded mesoporous calcium silicate nanoparticles against alkaline-resistant Enterococcus faecalis infection}},
author = {Runze Liu and Mengting Duan and Lian Bai and Zhongyuan Zhan and Yandi Dong and Yi Luo and Wei Fan},
journal = {Journal of Oral Microbiology},
year = {2026},
month = nov,
doi = {10.1080/20002297.2026.2753969},
url = {https://doi.org/10.1080/20002297.2026.2753969},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metformin-loaded mesoporous calcium silicate nanoparticles against alkaline-resistant Enterococcus faecalis infection
AU - Runze Liu
AU - Mengting Duan
AU - Lian Bai
AU - Zhongyuan Zhan
AU - Yandi Dong
AU - Yi Luo
AU - Wei Fan
PY - 2026
DA - 2026/11/07
JO - Journal of Oral Microbiology
DO - 10.1080/20002297.2026.2753969
UR - https://doi.org/10.1080/20002297.2026.2753969
AB - Background Enterococcus faecalis (E. faecalis) contributes to persistent endodontic infections through biofilm formation, dentinal tubule invasion, and alkaline resistance, which limits the efficacy of calcium hydroxide. Metformin (Met) attenuates this resistance by interfering with bacterial metabolic adaptation. Combining Met with mesoporous calcium silicate nanoparticles (MCSNs), which possess intrinsic alkaline antibacterial activity and sustained drug-delivery capabilities, may enhance the elimination of alkaline-resistant E. faecalis and promote periapical healing.Methods Metformin-loaded MCSNs (MCSNs-Met) were characterized for physicochemical properties, Met release, alkalinity, cytocompatibility, and dentinal tubule penetration. Antibiofilm activity against highly alkaline-resistant E. faecalis was assessed using infected dentin models. Therapeutic efficacy was further evaluated in a beagle model of E. faecalis-induced apical periodontitis using Micro-CT and histological analyses.Results MCSNs-Met exhibited a uniform mesoporous structure, sustained Met release and alkalinity, favorable cytocompatibility, and enhanced dentinal tubule penetration. Compared with MCSNs alone, MCSNs-Met more effectively disrupted E. faecalis biofilms and reduced viable bacterial signals. In vivo, MCSNs-Met produced the greatest reduction in periapical bone resorption, markedly decreased residual bacterial signals and inflammatory infiltration, reduced osteoclast activity, and enhanced collagen deposition and periapical tissue repair.Conclusions MCSNs-Met integrates sustained Met delivery with the intrinsic alkaline and bioactive properties of calcium silicate nanoparticles, thereby enhancing control of highly alkaline-resistant E. faecalis and promoting periapical healing.
SN - 2000-2297
ER -