Sphingosine-1-Phosphate Receptor Targeted PLGA Nanobubbles for Inflammatory Vascular Endothelial Cell Catching

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.