Magnetic ternary nanohybrids for nonviral gene delivery of stem cells and applications on cancer therapy

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.

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…Results showed that the transfection efficiency increased from 20% to 65% under the magnetic field attraction. In vivo experiments in Cg-Foxn1nu/CrlNarl mice confirmed suppression of human glioma (U87MG) by magnetic ternary nanohybrid-transfected TRAIL-expressing hMSCs [ 391 ].…”

In vivo gene delivery mediated by non-viral vectors for cancer therapy

“…Furthermore, Huang et al developed a superparamagnetic iron oxide NPs decorated with hyaluronic acid and functionalized with TNFrelated apoptosis-inducing ligand (TRAIL) and CD44. The complex significantly decreases the tumor size and enhanced survival rate in the orthotopic xenograft cancer BALB/cAnN.Cg-Foxn1nu/CrlNarl mice model [102].…”

New Insights into Biocompatible Iron Oxide Nanoparticles: A Potential Booster of Gene Delivery to Stem Cells

“…demonstrated that MSCs post gene transfection by using hyaluronic acid decorated SPIONs present a higher number of migrated cells at tumor sites when compared with none‐transfected MSCs. [ 30 ] However, this potential of IONPs seems is not universally workable for all cell types. For example, NeuroMag proved to have no impact on the migration of rat oligodendrocyte precursor cells.…”