Fused Membrane-Targeted Nanoscale Gene Delivery System Based on an Asymmetric Membrane Structure for Ischemic Stroke

<b>Background</b>: Bone marrow-derived mesenchymal stem cell exosomes (EXOs) are attractive in biotechnology and biomedical research, as they possess natural cell-targeting properties and can cross biological barriers by influencing the SDF-1/CXCR4 axis. Lipid calcium phosphate (LCP) consists of a calcium phosphate core and an asymmetric phospholipid bilayer containing abundant Ca²⁺ ions. AMD3100 modification of targeted LCP (T-LCP) can achieve targeted delivery to ischemic lesions via specific binding to CXCR4 receptors on various neuronal cell surfaces. <b>Methods</b>: Herein, a fused membrane formulation that simultaneously possesses EXO characteristics and enables targeted modification with AMD3100 was produced. The characteristics of biologically derived EXOs, artificially designed T-LCP, and the fused membrane formulation, including targeted delivery and gene loading efficiency, were then compared. <b>Results</b>: The fusion of artificially designed T-LCP with EXOs of natural origin is feasible and combines the advantages of both to achieve more prominent targeted delivery effects. <b>Conclusions</b>: MiRNA210-based gene therapy was effective in this study and provides a strategy for therapeutic efficacy in delivery systems with different targeting efficiencies.