H2O2–Sensitive Nanocarriers for In Vivo Antibiotic Delivery Targeting H2O2–Secreting Bacteria and Pulmonary Injury Treatment

In cases of pneumococcal pneumonia, there is significant exposure of the human airway epithelium to hydrogen peroxide (H2O2), a toxin secreted by pathogens. This exposure can trigger oxidative stress and enhance vascular permeability, which may result in systemic bacteremia or sepsis. Drug delivery systems (DDSs) that respond to H2O2 and utilize amphiphilic polymers have attracted considerable interest. In this study, we present an amphiphilic diblock copolymer (DPB) formed from poly(ethylene glycol) (PEG) and H2O2-sensitive phenylboronic ester (PBBA), capable of self-assembling into micelles in an aqueous environment. In this work, we demonstrated the efficacy of the spherical micelle DPB@(Amp+Cat), which encapsulates the antibiotic ampicillin (Amp) and the antioxidant catalase (Cat), for the treatment of H2O2-secreting bacterial pneumonia. Through triggering antibiotic release in response to H2O2 secreted by Streptococcus pneumoniae, DPB@(Amp + Cat) eliminated over 98% of the invading bacteria, leading to a survival rate exceeding 90% in mice with severe pneumonia. Furthermore, released catalase rapidly scavenges pneumococcal H2O2, resulting in reduced endothelial DNA damage and preventing the systemic invasion of bacteria. This work presents a synergistic strategy for both antipathogen treatment and pulmonary tissue protection in pneumococcal disease.