Engineering exosomes for pulmonary delivery of peptides and drugs to inflammatory lung cells by inhalation
Journal of Controlled Release(2021)
摘要
Exosomes have been investigated as delivery vesicles for various drugs. However, exosome-mediated peptide delivery into the lungs has not been studied. In this study, exosomes were engineered for the pulmonary delivery of RAGE-binding peptide (RBP), an anti-inflammatory peptide. To load the peptide into exosomes, RBP was linked to an exosome membrane integral protein, Lamp2b, to produce RBP-linked exosomes (RBP-exo). The anti-inflammatory effects of RBP-exo were confirmed by cytokine assays in lipopolysaccharide (LPS)-activated macrophage cells. To increase anti-inflammatory effects, curcumin was loaded into RBP-exo. Curcumin loaded RBP-exo (RBP-exo/Cur) had higher intracellular curcumin delivery efficiency than curcumin alone or curcumin loaded into unmodified exosomes (unmod-exo/Cur). This suggests that RBP on the surface of RBP-exo may interact with RAGE and increase the intracellular delivery efficiency of curcumin. In addition, RBP-exo/Cur had higher anti-inflammatory effects than curcumin alone, a mixture of RBP and curcumin, and unmod-exo/Cur in vitro. For in vivo evaluation, RBP-exo/Cur was administrated by intratracheal instillation into the lungs of an acute lung injury (ALI) model. The results showed that RBP-exo/Cur reduced pro-inflammatory cytokines more efficiently than curcumin alone, RBP-exo, and unmod-exo/Cur. Hematoxylin and eosin staining confirmed that the inflammation reaction was inhibited in the RBP-exo and RBP-exo/Cur groups. Immunostaining assays showed that RBP-exo was co-localized mostly with type I epithelial cells. In conclusion, RBP was successfully delivered with exosomes into the lungs by inhalation. A combination of RBP and curcumin using exosomes as carriers may be useful as ALI therapy.
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关键词
Acute lung injury,Curcumin,Exosomes,Pulmonary delivery,RAGE-binding peptide
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