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.