Antisense Oligonucleotide-Capped Gold Nanoparticles as a Potential Strategy for Tackling Antimicrobial Resistance

Multidrug-resistant (MDR) bacterial pathogens pose a serious threat to global health, underscoring the urgent need for innovative therapeutic strategies. In this work, we designed and characterized thiol-modified antisense oligonucleotide-capped gold nanoparticles (ASO-AuNPs) to resensitize antibiot...

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Main Authors: Cesar Rodolfo Garza-Cardenas, Angel Leon-Buitimea, A. A. Siller-Ceniceros, Jose Ruben Morones-Ramirez
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Microbiology Research
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Online Access:https://www.mdpi.com/2036-7481/16/3/70
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Summary:Multidrug-resistant (MDR) bacterial pathogens pose a serious threat to global health, underscoring the urgent need for innovative therapeutic strategies. In this work, we designed and characterized thiol-modified antisense oligonucleotide-capped gold nanoparticles (ASO-AuNPs) to resensitize antibiotic-resistant bacteria. Transmission electron microscopy and UV–Vis spectroscopy confirmed the morphology, size, and optical properties of AuNPs and ASO-AuNPs. Minimum inhibitory concentrations (MIC) of ampicillin were determined for non-resistant <i>Escherichia coli</i> DH5α (16 ppm) and an ampicillin-resistant <i>E. coli</i> DH5α strain (PSK, 32,768 ppm). When co-administered with ampicillin, ASO-AuNPs (0.1 and 0.2 nM) significantly reduced bacterial growth compared to the antibiotic-alone control (<i>p</i> < 0.05), demonstrating the capacity of ASO-AuNPs to restore antibiotic efficacy. These findings provide a proof of concept that antisense oligonucleotide-functionalized nanomaterials can be harnessed to overcome beta-lactam resistance, setting the stage for further optimization and translation into clinical applications.
ISSN:2036-7481