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Abstract Drug‐resistant microorganisms cause serious problems in human healthcare, leading to the persistence in infections and poor treatment outcomes from conventional therapy. In this study, a gene‐targeting strategy using microbubble‐controlled nanoparticles is introduced that can effectively eliminate biofilms of methicillin‐resistantStaphylococcus aureus(MRSA) in vivo. Biofilm‐targeting nanoparticles (BTN) capable of delivering oligonucleotides are developed that effectively remove biofilm‐associated bacteria upon controlled delivery with diatom‐based microbubblers (MB). The activity of BTN in silencing key bacterial genes related to MRSA biofilm formation (icaA), bacterial growth (ftsZ), and antimicrobial resistance (mecA), as well as their multi‐targeting ability in vitro is validated. The integration of BTN with MB is next examined, resulting in synergistic effects in biofilm removal and antimicrobial activity in an ex vivo porcine skin model. The therapeutic efficacy is further investigated in vivo in a mouse wound model infected with MRSA biofilm, which showed that MB‐controlled BTN delivery substantially reduced bacterial load and led to the effective elimination of the biofilm. This study underscores the potential of the gene silencing platform with physical enhancement as a promising strategy to combat problems related to biofilms and antibiotic resistance.
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Superparamagnetic nanoparticles for the treatment of periodontal disease
Periodontal diseases are prevalent worldwide and are linked to numerous other health conditions due to dysbiosis and chronic inflammatory state. Most periodontal diseases are caused by pathogenic bacteria that colonize dental tissues in the form of biofilm. Eradication of bacterial biofilms can be difficult to achieve due to the complex architecture of the teeth and gums which complicates the removal. Orthodontic wires and dental devices introduce additional hurdles to the adequate removal of biofilms by traditional methods since mechanical disruption via direct contact with toothbrush bristles, floss, and abrasive toothpaste is limited. Magnetically activated nanoparticles (NPs), specifically iron oxide nanoparticles (IONPs) that can be functionalized as antimicrobial particles and remotely controlled by magnetic fields, are of interest for oral biofilm eradication. We present data in multi-species bacterial cultures, established biofilms, human gingival keratinocytes, and human gingival fibroblast cells alone and in the presence of multispecies biofilm co-cultures to determine the safest, most efficacious IONP size ranges and treatment concentrations of active magnetic NPs for removal of dental biofilms. We report enhanced efficacy for IONPs coated with alginate vs. dextran, and small sizes (~8 nm vs. >20 nm in size) appear to exhibit enhanced antimicrobial efficacy. Human gingival keratinocyte (TIGK) cells in co-culture with treated and untreated multispecies biofilms in an in-vitro periodontitis model also exhibited a trend of reduced inflammatory markers in wells with IONP-treated biofilms.
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- Award ID(s):
- 2151653
- PAR ID:
- 10421777
- Editor(s):
- Osiński, Marek; Kanaras, Antonios G.
- Date Published:
- Journal Name:
- Colloidal Nanoparticles for Biomedical Applications XVIII
- Volume:
- 12395
- Page Range / eLocation ID:
- 50-59
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Conference Paper:
- https://doi.org/10.1117/12.2654656
