Silica-coated superparamagnetic iron oxide nanoparticles targeting of EPCs in ischemic brain injury

Abstract

Intravenous transplantation of endothelial progenitor cells (EPCs) reduced ischemic brain injury. However, less cell homing to damaged sites limited its functions. In present study, we labeled EPCs with silica-coated superparamagnetic iron oxide nanoparticles (SiO4@SPIONs) and applied exterior magnetic field to guide SiO4@SPIONs-labeled EPCs (SiO4@SPIONs-EPCs) to the ischemic hemisphere of the brain. We optimized SiO4@SPIONs labeling dose, which did not affect proliferation, migration and tube formation of EPCs in vitro. SiO4@SPIONs-EPCs homing was greatly increased in ischemic hemisphere with magnetic field treatment in mice underwent transient middle cerebral artery occlusion (tMCAO). Injection of SiO4@SPIONs-EPCs and followed by magnetic field treatment showed improved neurobehavioral outcomes, reduced brain atrophic volume, increased microvessel density and VEGF expression in the ischemic perifocal region compared to groups without magnetic field treatment (p < 0.05). Our results demonstrated that exterior magnetic field could guide SiO4@SPIONs-EPCs to ischemic region and enhance therapeutic effect, suggesting that magnetic-guided SiO4@SPIONs-EPCs delivery is a promising approach in cerebral ischemic therapy.