ROS responsive polydopamine coated black phosphorus nanocarrier for enhanced methylprednisolone delivery in acute lung injury immunotherapy

Acute lung injury (ALI) is a serious lung disease typically caused by excessive inflammatory reactions in the lung. This study aimed to reprogram the lung redox homeostasis for ALI immunotherapy. To address this, a novel polydopamine (PDA) coated black phosphorus nanocarrier (BP@P + MP) was prepared through π-π conjugation and hydrogen bonding between methylprednisolone (MP) and PDA. It was found that BP@P + MP possessed excellent reactive oxygen species (ROS) scavenging abilities, and ROS responsiveness to achieve the controllable release of MP. For lipopolysaccharide induced macrophages and ALI rat models, BP@P + MP could effectively lower intracellular ROS levels, decrease iNOS and IL-1β expression levels, promote Arg-1, IL-10 and HSP70 expression levels, induce macrophage M2 polarization and T cells immunoactivation, and inhibit NF-κB pathway. It finally demonstrated the function of reprogramming lung microenvironment, and promoting lung tissue repair to alleviate ALI. Significantly, following aerosol nebulization (AN), BP@P could retain in the lung for 12 h, and gradually be cleared versus time. This work had designed a novel ROS responsive drug carrier for the synergistic ALI immunotherapy, which may serve as a promising therapeutic strategy for other inflammation related diseases.