Abstract
Cancer toxic agent-expressing mesenchymal stem cells (MSCs), which possess inherent tumor migration and penetration capabilities, have received increasing attention in cancer therapy. To ensure that this approach is successful, safe and efficient gene delivery methods for stem cell engineering must be developed. Methods: In this study, a magnetic ternary nanohybrid (MTN) system comprising biodegradable cationic materials, nucleic acids, and hyaluronic acid-decorated superparamagnetic iron oxide nanoparticles was proposed to construct stem cells expressing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via magnetic force and receptor dual targeting. Results: The CD44/magnetic force-mediated enhanced cellular uptake of MTNs by human mesenchymal cells (hMSCs) was confirmed in vitro. Highly efficient transfection was attained using MTNs without having any detrimental effect on the tumor migration and penetration capabilities of hMSCs. TRAIL expressed by the MTN-transfected hMSCs displayed strong anticancer effects through the activation of caspase-3 apoptotic signaling. The MTN-transfected hMSCs can be clearly imaged using magnetic resonance imaging techniques in vivo. In an orthotopic xenograft cancer model, MTN-transfected TRAIL-expressing hMSCs significantly suppressed the progression of human glioma (U87MG) and prolonged the survival of the animal. Conclusions: These findings suggest the considerable potential of utilizing MTNs for effectively constructing tumor toxic agent-expressing stem cells for treating malignant cancers.