Enhanced Targeted Repair of Vascular Injury by Apoptotic-Cell-Mimicking Nanovesicles Engineered with P-Selectin Binding Peptide

Abstract

Modulating inflammation is crucial for repairing vascular injury. Phagocytosis of apoptotic cells represents an effective mechanism for attenuating inflammation and improving regeneration during natural healing. However, strategies for repairing vascular injuries using biomaterials derived from apoptotic cells are still undeveloped. Herein, apoptotic body-mimetic nanovesicles (ApoNVs) derived from rat adipose-derived mesenchymal stem cells (rASCs) are prepared using a one-step extrusion method. ApoNVs inherit the unique anti-inflammatory and pro-regenerative properties of the parental apoptotic rASCs, as evidenced by enhanced M2 polarization of macrophages and promoted endothelial cell proliferation and migration following treatment with ApoNVs. Moreover, ApoNVs enhance the contractile phenotype of vascular smooth muscle cells through the mediation of ApoNVs-induced repolarized macrophages. After engineering ApoNVs with P-selectin binding peptide (ApoNVs-PBP), their ability to target injured artery increased nearly sevenfold compared to unmodified ApoNVs. In a rat wire-mediated femoral artery injury model, ApoNVs-PBP effectively suppress inflammation and significantly reduce blood flow velocity and neointimal hyperplasia at the injury site. ApoNVs exhibit similar therapeutic effects, though to a lesser extent. This study provides strong evidence validating the targeted delivery of ApoNVs as an innovative approach for repairing vascular injury and highlights their potential in treating other inflammatory diseases.