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 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 Escherichia coli DH5α (16 ppm) and an ampicillin-resistant E. coli 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 (p < 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.