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 (H 2 O 2 ), 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 H 2 O 2 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 H 2 O 2 -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 H 2 O 2 -secreting bacterial pneumonia. Through triggering antibiotic release in response to H 2 O 2 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 H 2 O 2, 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.