"Gold nanoparticle-based nanotheranostics for combating global antimicrobial resistance: a docking-guided multifunctional approach"

Antimicrobial resistance has expanded globally, reducing the efficacy of antimicrobial drugs and increasing the incidence of severe effects and death. In this context, nanotechnology combined with natural flavonoids like Quercetin has become a key strategy to combat antimicrobial resistance due to their unique physiochemical properties and antibacterial effects. Therefore, in this study, smart nanotheranostics comprising gold nanoparticles conjugated with quercetin have been developed to achieve image-guided antibacterial therapy. The nanoformulations were synthesized using a chemical technique, and monodispersed, stable, biocompatible nanoparticles with a high conjugation efficacy rate (96%) were achieved. Further, the conjugated formulation showed a biphasic drug release pattern. The cellular uptake study of gold nanoparticles by fluorescence microscopy was performed to understand the imaging applications of the developed formulations. Antimicrobial assays, such as % inhibition, where Qe-AuNPs showed 72% ± 0.5 and 65% ± 0.5, minimum inhibitory concentration exhibited 2.5 ± 0.4µg/mL and 10± 0.17µg/mL, and GSH activity dropped to 58.78% and 87.5%, against two AMR bacterial strains Staphylococcus aureus and Pseudomonas aeruginosa respectively. These results showed that quercetin-conjugated gold nanoparticles were more effective than quercetin. Furthermore, the live-dead staining assay provided important insights into the mechanism of action of quercetin-conjugated gold nanoparticles, where concentration-dependent activity was observed. Overall, the results suggest the enhanced antibacterial activity of quercetin-conjugated gold nanotheranostics. In the end, in-silico analysis further confirms Quercetin's favourable binding to Sortase A and Elastase B, confirming the effective suppression of both strain's pathogenicity by quercetin-conjugated gold nanoparticles. As a result, synthesized nanoformulations have shown a unique framework for merging multiple therapeutic and imaging modalities into a single nanoplatform to tackle antibiotic resistance in the future. .