Nitric oxide-assisted mucus-walking zwitterionic nanocomplexes for synergistic treatment of severe respiratory infectious disease

Abstract

Among patients who suffer from lung-related disability, acute respiratory distress syndrome (ARDS) is one of the diseases with the significant mortality rate and the main cause is the interference in pulmonary drug delivery by accumulated bronchoalveolar lavage fluid (BALF) in the alveolar region. Here, a zwitterion-functionalized multi-drug nanocomplex (ZnC) capable of anti-mucociliary clearance was synthesized. Additionally, nitric oxide (NO) was functionalized with ZnC to fuel the mobility in the BALF through its role as a nanomotor as well as anti-inflammation. Subsequently, dexamethasone (Dex) was loaded and final product of anti-inflammatory mucus permeator (AIM) was introduced. By in situ tracking the AIM within the mucus-rich environment, the fueled mobility by NO and zwitterion was demonstrated. Notably, when AIM was inhaled by the in vivo ARDS model, there was an increase in the anti-inflammation effect due to the presence of ZnC as well as the synergy between NO and Dex, which recovered the pulmonary function of the model and increased survival rate.