ROS-Responsive Poly(α-l-lysine)-Based Nanoparticles Loaded with Doxycycline Combat Oxidative Stress and Bacterial Infection.

Abstract

Bacterial pneumonia is one of the major threats in clinical practice, and the reactive oxygen species (ROS) generated at the infection site can exacerbate the damage. Currently, conventional antibiotic therapies have low utilization, and their excessive use can result in substantial toxicity. Nanocarrier systems provide an ideal approach for treating bacterial infection by facilitating more efficient utilization of antibiotics. In this study, the ROS-responsive amphiphilic nanoparticles (NPs) are developed and used to encapsulate the antibiotic doxycycline (DOXY) to achieve antibacterial and antioxidant functionalities. The NPs are prepared from poly(α-l-lysine) (α-PLL) and phenylboronic acid pinacol ester simultaneously conjugated carbonyldiimidazole (abbreviated as CDIPB). The phenylboronic acid ester groups on CDIPB could react with excessive ROS to suppress oxidative damage at the infection site. The ROS-responsive degradation of CDIPB also facilitates the rapid release of internal DOXY, effectively killing the accumulated bacteria. Additionally, in vitro cell experiments demonstrate the good biocompatibility of the NPs. These results suggest that the ROS-responsive amphiphilic nanoparticles can serve as a novel nanoplatform for the treatment of bacterial pneumonia.