A self-assembled and H₂O₂-activatable hybrid nanoprodrug for lung infection and wound healing therapy

Background: The pursuit of effective antibacterial strategies aimed at mitigating pathogenic bacterial infections while minimising drug resistance remains of paramount importance. A combinational therapeutic strategy that integrates distinct treatment components can enhance overall efficacy and mitigate undesired effects, thereby exhibiting considerable promise in combating bacterial infections. Methods: In this study, a meticulously engineered self-assembling hybrid nanoprodrug (CPBP NPs) has been devised, functioning as a hybrid prodrug of Ciprofloxacin (Cip) and hydroxybenzyl alcohol (HBA). Results: CPBP molecules can generate nanoassemblies via self-assembly and subsequently undergo decomposition to synchronously release Cip and HBA upon hydrogen peroxide (H₂O₂) exposure. The CPBP NPs exert antibacterial and anti-inflammatory properties through the controlled release of Cip and HBA, while also facilitating the scavenging of reactive oxygen species. These CPBP NPs exhibit broad-spectrum antibacterial activity against both Gram-negative bacteria (E. coli, 98.4%) and Gram-positive bacteria (S. aureus, 98.5%). Notably, CPBP NPs not only accumulate in the lungs to facilitate organ-specific infection treatment but also expedite the healing process of infected wounds. Conclusions: Consequently, this H₂O₂-activatable hybrid nanoprodrug, possessing excellent biocompatibility, holds substantial promise for advancing clinical applications in managing bacterial infections.