Related Experiment Video
Updated: Aug 14, 2026
Neuron-Macrophage Co-cultures to Activate Macrophages Secreting Molecular Factors with Neurite Outgrowth Activity
Published on: March 30, 2018
GNPs-pIL-4 reprograms macrophage polarization and activates the OSM/GSNOR/ENG axis to improve angiogenesis in
Peng Zhang1,2,3, Jinman Zhuang1, Yizhou Hao4
1Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Department of Interventional Radiology and Vascular Surgery, Third Hospital, Peking University, Beijing, China.
None:
Therapeutic angiogenesis based on gene therapies is a potential peripheral artery disease (PAD) treatment yet needs a more stable, efficient, and high-affinity delivery vector and an optimized delivery strategy. Here, we engineered three-dimensional graphene nanoparticles modified with folic acid and polyethyleneimine for macrophage-specific delivery of interleukin-4 plasmids (pIL-4), forming GNPs-pIL-4 for local intramuscular injection. GNPs-pIL-4 had uniform size, positive surface charge, and strong nucleic acid loading capacity (Kd: 25 nanomolar). In vivo, GNPs-pIL-4 reshaped the ischemic microenvironment by inducing reparative M2 macrophage polarization. Mediated by macrophages, GNPs-pIL-4 improved muscle contractility, delayed strength loss, and enhanced blood perfusion and oxygen saturation. Mechanistically, GNPs-pIL-4 specifically turned on the oncostatin M-mediated macrophage-endothelium communication and then activated the angiogenesis, with increased endothelial sprouting, migration, and tube formation. These effects attributed to the down-regulated S-nitrosoglutathione reductase expression, thereby increasing S-nitrosylation at the C209 site of endoglin. GNPs-pIL-4 represents a promising gene therapy strategy for PAD.
