Metal-Responsive Fluorophore and Amikacin-Conjugated Heparin for Bacterial Cell Imaging and Antibacterial Applications.

Abstract

The escalating prevalence of bacterial infections presents a formidable challenge to current global healthcare systems. Rapid identification and quantification of bacterial pathogens with anticipated sensitivity and selectivity are crucial for targeted therapeutic interventions to mitigate disease burden, drug resistance, and further transmission. Concurrently, there is a pressing need to innovate novel approaches to combat infections and counter antibiotic resistance. Herein, we demonstrated the development of heparin (HP) conjugates modified with a Zn²⁺-induced "turn-on" fluorophore, 2-(pyridin-2-yl)-1H-benzo[d]imidazole (PBI), that interacts with bacterial cells via specific binding with the surface-exposed heparin-binding proteins (HPBs), thereby inducing fluorescence signals for rapid and selective sensing of whole bacterial cells. Additionally, amikacin (Amk) antibiotic was integrated into the modified heparin polymer (HP-PBI-Amk) to augment its antibacterial efficacy via reactive oxygen species generation. Despite the nephrotoxicity of only amikacin, its inclusion in the biopolymer retains its antibacterial properties while providing biocompatibility. The outcome of this study demonstrates the development of HP-PBI and HP-PBI-Amk as promising strategies for bacterial detection and eradication, respectively, offering potential avenues for future research and clinical applications.