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

## TL;DR

This paper introduces a new gene delivery system combining exosomes and a modified lipid structure to target ischemic stroke areas more effectively.

## Contribution

The novel fused membrane system integrates natural exosome properties with AMD3100-modified lipid structures for enhanced targeted gene delivery.

## Key findings

- Fusing T-LCP with exosomes achieves better targeted delivery to ischemic lesions.
- The system combines natural and artificial components to improve gene delivery efficiency.
- MiRNA210-based gene therapy showed effectiveness in stroke treatment using this system.

## Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: MiRNA210-based gene therapy was effective in this study and provides a strategy for therapeutic efficacy in delivery systems with different targeting efficiencies.