Remotely Triggered Activation of TGF- With Magnetic Nanoparticles

Growth factors or cytokines have demonstrated the potential to alter and manipulate the biological activity of cells via binding and activation of cell surface receptors. Changes induced by cytokines can range from simple changes in the cellular motility and proliferation to more complex biological actions, such as stem-cell differentiation. Transforming growth factor beta (TGF-β) exhibits the typical functionality of a growth factor, as it is pleiotropic and causes myriad responses in a number of cell types. This multifunctional nature gives the TGF-β a great potential for therapeutic applicationsparticularly in regenerative medicine. However, this multifunctionality till now has limited its usage in vivo, since upon injection, the cytokine may activate nefarious signaling pathways, such as those associated with tumor formation. In addition to this problem, the short half-lives of cytokines also places constraints on their delivery, as the majority of the injected biomolecule will not have a sufficient biological lifetime to reach the desired target location. Therefore, the methods of targeting the growth factors to specific sites in the body will prove crucial to their successful clinical implementation. Here, we describe a novel growth-factor targeting and activation strategy based on the delivery of energy from external alternating magnetic fields to magnetic nanoparticles to which a latent TGF-β has been conjugated. We demonstrate the successful conjugation of a latent TGF-β to the surface of poly(ethylene glycol)-coated iron oxide nanoparticles, and subsequent triggered release of an active TGF-β from its latent complex on the application of an external radio frequency magnetic field. This preliminary study highlights the potential of magnetic activation to remotely control the TGF-β activity in vivo, reducing the dangerous off-target side effects and offering a path to clinical implementation of this growth factor fo- regenerative medicine applications.