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Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are life-threatening lung diseases with extremely high mortality rates. There are still limited effective and safe treatment strategies for these conditions. There is an urgent need to develop targeted and biocompatible drug delivery systems to control the inflammatory cascade in the lungs while minimizing systemic toxicity. Plant-derived extracellular vesicles provide a naturally safe and anti-inflammatory platform for therapeutic delivery. Ginsenoside Rb1 (GRb1), a major bioactive compound derived from ginseng, has potent anti-inflammatory and anti-apoptotic properties, while lemon-derived EVs (LEVs) have intrinsic antioxidant and anti-inflammatory effects. We designed a multifunctional and biocompatible drug delivery platform, GRb1@LEVs-cRGD, in which GRb1 is integrated and fused with LEVs to form a mixed biologic nanocapsule, and the surface of the capsule is functionalized with cyclic RGD (cRGD) peptide to target highly expressed integrin αvβ3 in inflammatory lung tissue, thereby enhancing site-specific delivery. In vitro and in vivo studies have confirmed that GRb1@LEVs-cRGD effectively inhibits M1 macrophage polarization, suppresses the inflammatory cascade, and maintains epithelial-endothelial integrity. Additionally, exogenous cholesterol load enhances the stability of the vesicles, maintains the pH gradient, and increases the loading efficiency of tigecycline and vancomycin by six times. In a mouse model of bacterial pneumonia induced by carbapenem-resistant Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus, the antibiotic-loaded GRb1@LEVs-cRGD efficiently accumulates at the infection site and exhibits synergistic anti-inflammatory and bactericidal effects. Overall, our study demonstrates that GRb1@LEVs-cRGD is a safe, targeted, and multifunctional therapeutic platform with significant potential for the treatment of ALI/ARDS.
This study was published in Bioactive Materials under the title "A safe and anti-inflammatory plant-derived nanovesicle platform for targeted delivery in acute lung injury".
References:
DOI: 10.1016/j.bioactmat.2026.03.03
