pH/ROS Dual-Responsive Zwitterionic Polymer Micelles with Enhanced Mucus Penetration for Bacterial Pneumonia Therapy

Bacterial pneumonia, a prevalent respiratory disease with high global morbidity and mortality rates, remains a formidable therapeutic challenge. Herein, pH/reactive oxygen species (ROS) dual-responsive zwitterionic polymer (PODEA-b-P(ROS-CA-EG)n) micelles are developed for bacterial pneumonia therapy. The zwitterionic shell can facilitate the micelles to effectively penetrate through the mucus. These micelles exhibit pH-responsive charge reversal performance, which is conducive to the cellular internalization and bacterial killing. Meanwhile, the micelles respond to the acid and overexpressed ROS microenvironment at the lesion site to release cinnamaldehyde (CA), enhance ROS generation, and activate an immune reaction to eliminate extracellular and intracellular bacteria collaboratively. In bacterial pneumonia, PODEA-b-P(ROS-CA-EG)n micelles can effectively eliminate bacteria and alleviate lung inflammation. These pH/ROS dual-responsive zwitterionic polymer micelles could provide a synergistic therapeutic strategy against bacterial pneumonia.