Immuno-protective cationic ginsenoside Rb1 vesicles for macrophage-mediated targeted therapy of inflammatory diseases

Inflammatory diseases (IDs), characterized by chronic inflammation, are linked to conditions such as bacterial and viral infections, arthritis, and neurodegenerative disorders. Current treatments offer only temporary relief, highlighting the need for more effective therapies. Ginsenoside Rb1 (Rb1), with potent anti-inflammatory and antioxidant properties, can self-assemble into nanoparticles. To enhance targeted therapy for IDs, this study explores the effects of cationic modifications on Rb1 self-assemblies (GRb1). Among the various modifications, polyethylenimine (PEI) (GRb1@PEI) is the most effective at enhancing GRb1's ability to specifically target macrophages. In a murine model of LPS-induced sepsis-related acute lung injury (ALI), PEI facilitates the delivery of Rb1 to sites of inflammation. There, Rb1 inhibits the TNF-α signaling pathway, which helps normalize inflammatory markers and reduce immune cell recruitment. Additionally, GRb1@PEI serves as a multifunctional carrier for antibiotics with diverse physicochemical properties, enhancing bacterial clearance and alleviating inflammation and immune responses in blood infection-associated ALI and bacterial pneumonia models. Among four cationic polymer-modified GRb1 variants, this study demonstrates that GRb1@PEI is the most efficient multifunctional nanocarrier for targeted anti-inflammatory therapy of inflammatory diseases, providing important guidance for future therapeutic development.