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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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This content will become publicly available on November 13, 2026
Using a bacterial protein to selectively target bacterial biofilms: Treatment of S. epidermidis biofilms with targeted Photothermal gold nanoparticles
Biofilm-related infections are associated with high mortality and morbidity combined with increased treatment costs. Traditional antibiotics are becoming less effective due to the emergence of drug-resistant bacterial strains. The need to treat biofilms on medical implants is particularly acute, and one persistent challenge is selectively directing nanoparticles to the biofilm site. Here, we present a protein-based functionalization strategy that targets the extracellular matrix of biofilms. The engineered protein combines the Staphylococcus epidermidis autolysin R2ab domain with a gold-binding GB3 domain, directing nanoparticles specifically to bacterial cell wall components (lipoteichoic acid and wall teichoic acid) that are absent in mammalian tissues. This fusion protein is applied to a gold nanoparticle (AuNP) core, along with elastin-like polypeptides (ELPs), which generate a robust photothermal response. The engineered particles exhibit exceptional biocompatibility, including low protein corona formation, minimal macrophage uptake, and hemocompatibility, while maintaining selective biofilm targeting. The photothermal conversion can be modulated by changing the ELP transition temperature, and the functionalized AuNPs strongly interact with biofilms under static and flow conditions without significantly binding to serum-coated surfaces. Near-infrared laser irradiation resulted in a 10,000-fold improvement in killing efficiency compared to untreated controls (p < 0.0001). The targeting strategy utilized here represents a versatile approach to targeting drug-resistant infections and could be readily expanded to other bacterial pathogens and anti-biofilm nanoparticle platforms.
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- PAR ID:
- 10647329
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Journal of colloid and interface science
- ISSN:
- 0021-9797
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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