Targeting macrophage polarization with opsonized bilirubin/melatonin nanoparticles: A biomimetic approach for acute...

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by non-cardiogenic pulmonary edema, hypoxic respiratory failure, reduced functional residual capacity, decreased lung compliance, non-hydrostatic bilateral pulmonary infiltrates, and increased vascular permeability due to protein-rich exudates and neutrophil infiltration in the alveolar spaces. ALI/ARDS is associated with high mortality due to poor prognosis, lack of effective therapies, and prolonged hospitalization. Macrophages play a pivotal role in modulating the inflammatory response during ALI/ARDS, with M1 macrophages initiating severe inflammation and lung damage while M2 macrophages regulate tissue repair. Targeting macrophage polarization is a promising therapeutic approach for alleviating tissue damage and promoting resolution in ALI/ARDS. In response to this, we developed novel self-assembling carrier-free nanoparticles, bilirubin (BR) and melatonin (MT), with surface-adsorbed immunoglobulin G (IgG), referred to as IgG@BMNP. These nanoparticles are designed to target M1 macrophages in the lungs of ALI model mice. Under oxidative stress, IgG@BMNP disintegrate, releasing BR and MT, which scavenge excess reactive oxygen species (ROS) in the lungs and inhibit overactivation of the NLRP3 inflammasome, thereby promoting macrophage polarization from the M1 to the M2 phenotype. In ALI model mice, IgG@BMNP effectively alleviate lung injury, demonstrating potential as a therapeutic approach for ALI. This opsonization strategy, which involves M1 macrophages engulfing carrier-free IgG@BMNP to suppress inflammation, shows promising potential for the treatment and management of ALI/ARDS.