Versatile Design of NO‐Generating Proteolipid Nanovesicles for Alleviating Vascular Injury

Abstract Vascular injury is central to the pathogenesis and progression of cardiovascular diseases, however, fostering alternative strategies to alleviate vascular injury remains a persisting challenge. Given the central role of cell‐derived nitric oxide (NO) in modulating the endogenous repair of vascular injury, NO‐generating proteolipid nanovesicles (PLV‐NO) are designed that recapitulate the cell‐mimicking functions for vascular repair and replacement. Specifically, the proteolipid nanovesicles (PLV) are versatilely fabricated using membrane proteins derived from different types of cells, followed by the incorporation of NO‐generating nanozymes capable of catalyzing endogenous donors to produce NO. Taking two vascular injury models, two types of PLV‐NO are tailored to meet the individual requirements of targeted diseases using platelet membrane proteins and endothelial membrane proteins, respectively. The platelet‐based PLV‐NO (pPLV‐NO) demonstrates its efficacy in targeted repair of a vascular endothelium injury model through systemic delivery. On the other hand, the endothelial cell (EC)‐based PLV‐NO (ePLV‐NO) exhibits suppression of thrombosis when modified onto a locally transplanted small‐diameter vascular graft (SDVG). The versatile design of PLV‐NO may enable a promising therapeutic option for various vascular injury‐evoked cardiovascular diseases.