Abstract
Vascular inflammation is an early manifestation and common pathophysiological basis of numerous cardiovascular and cerebrovascular diseases. However, effective surveillance methods are lacking. In this study, sulfur hexafluoride (SF6 )-loaded polylactic acid-co-glycolic acid (PLGA) nanobubbles (NBs) with a surface assembly of cyclodextrin (CD) and sphingosine-1-phosphate (S1P) (S1P@CD-PLGA NBs) are designed. The characterization results show that S1P@CD-PLGA NBs with diameters of ≈200 nm have good stability, biosafety, and ultrasound imaging-enhancement effects. When interacting with inflammatory vascular endothelial cells, S1P molecules encapsulated in cyclodextrin cavities exhibit a rapid, excellent, and stable targeting effect owing to their specific interaction with the highly expressed S1P receptor 1 (S1PR1) on the inflammatory vascular endothelial cells. Particularly, the S1P-S1PR1 interaction further activates the downstream signaling pathway of S1PR1 to reduce the expression of tumor necrosis factor-α (TNF-α) to protect endothelial cells. Furthermore, mouse models of carotid endothelial injuries and mesenteric thrombosis demonstrate that S1P@CD-PLGA NBs have excellent capabilities for in vivo targeting imaging. In summary, this study proposes a new strategy of using S1P to target inflammatory vascular endothelial cells while reducing the expression of TNF-α, which has the potential to be utilized in the targeted surveillance and treatment of vascular inflammatory diseases.