Adenosine triphosphate-activated prodrug system for on-demand bacterial inactivation and wound disinfection

The prodrug approach has emerged as a promising solution to combat bacterial resistance and enhance treatment efficacy against bacterial infections. Here, we report an adenosine triphosphate (ATP)-activated prodrug system for on-demand treatment of bacterial infection. The prodrug system benefits from the synergistic action of zeolitic imidazolate framework-8 and polyacrylamide hydrogel microsphere, which simultaneously transports indole-3-acetic acid and horseradish peroxidase in a single carrier while preventing the premature activation of indole-3-acetic acid. The ATP-responsive characteristic of zeolitic imidazolate framework-8 allows the prodrug system to be activated by the ATP secreted by bacteria to generate reactive oxygen species (ROS), displaying exceptional broad-spectrum antimicrobial ability. Upon disruption of the bacterial membrane by ROS, the leaked intracellular ATP from dead bacteria can accelerate the activation of the prodrug system to further enhance antibacterial efficiency. In vivo experiments in a mouse model demonstrates the applicability of the prodrug system for wound disinfection with minimal side effects. Prodrugs are increasingly promising in tackling bacterial resistance and efficacy of treatment. Here, the authors encapsulated horseradish peroxidase and zeolitic imidazolate framework-8 loaded with indole-3-acetic acid in polyacrylamide hydrogel microspheres for ATP-activated wound disinfection.

Automated summary

This study presents an ATP-activated prodrug system for on-demand treatment of bacterial infections. The system utilizes zeolitic imidazolate framework-8 and polyacrylamide hydrogel microspheres to transport indole-3-acetic acid and horseradish peroxidase, preventing premature activation of the prodrug. The ATP-responsive characteristic of zeolitic imidazolate framework-8 allows the system to be activated by bacterial-secreted ATP, generating reactive oxygen species for broad-spectrum antimicrobial ability. The leaked intracellular ATP from dead bacteria further enhances the activation of the prodrug system. In vivo experiments show the applicability of the system for wound disinfection with minimal side effects.