Magnetic Control of Protein Expression via Magneto-mechanical Actuation of ND-PEGylated Iron Oxide Nanocubes for Cell Therapy

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Engineered cells used as smart vehicles for delivery of secreted therapeutic proteins enable effective treatment of cancer and certain degenerative, autoimmune, and genetic disorders. However, current cell-based therapies use mostly invasive tools for tracking proteins and do not allow for controlled secretion of therapeutic proteins, which could result in unconstrained killing of surrounding healthy tissues or ineffective killing of host cancer cells. Regulating the expression of therapeutic proteins after success of therapy remains elusive. In this study, a noninvasive therapeutic approach mediated by magneto-mechanical actuation (MMA) was developed to remotely regulate the expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein, which is secreted by transduced cells. Stem cells, macrophages, and breast cancer cells were transduced with a lentiviral vector encoding the SGpL2TR protein. SGpL2TR comprises TRAIL and GpLuc domains optimized for cell-based applications. Our approach relies on the remote actuation of cubic-shape highly magnetic field responsive superparamagnetic iron oxide nanoparticles (SPIONs) coated with nitrodopamine PEG (ND-PEG), which are internalized within the cells. Cubic ND-PEG-SPIONs actuated by superlow frequency alternating current magnetic fields can translate magnetic forces into mechanical motion and in turn spur me

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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