Armored polymyxin B: a nanosystem for combating multidrug-resistant Gram-negative bacilli

Abstract

Bacterial infections cause high morbidity and mortality worldwide, and the emergence of drug-resistant bacteria further complicates the treatment of infections. Therefore, it is necessary to continuously develop new treatment methods. Polymyxin B (PMB), as the last line of defense, can combat most aerobic Gram-negative bacilli including common drug-resistant bacteria in clinical practice. However, the suboptimal lung tissue concentration of PMB and dose-dependent nephrotoxicity and neurotoxicity limit its clinical application. The nanodrug delivery system offers several key advantages, including high drug loading capacity, excellent biocompatibility, controlled release mechanisms, and targeted delivery. These features enhance the bioavailability of drugs while simultaneously reducing their toxicity and minimizing side effects. In this study, we designed a targeted nanodrug delivery system (PMB@HMnO₂@NM) consisting of hollow mesoporous manganese dioxide (HMnO₂) coated with neutrophil membrane (NM). In a mouse model of acute pneumonia induced by multidrug-resistant Pseudomonas aeruginosa, treatment with PMB@HMnO₂@NM demonstrated the ability to target bacterial aggregation and specifically deliver the drug to the infected lung tissue. This targeted approach resulted in improved survival rates and reduced inflammatory damage without causing adverse effects. The findings of this study suggest the potential for developing a new class of multifunctional nanodrugs, providing new therapeutic strategies for multidrug-resistant (MDR) bacterial infections. Furthermore, these results provide a solid foundation for the design of biomimetic nanosized antibacterial drugs.