Cellular Engineering for the Remote-Controlled Delivery of Therapeutics

Stem cells have a number of useful properties, including their ability to proliferate, migrate and differentiate. For this reason, numerous clinical studies have utilized stem cell-based therapies for the treatment of various human diseases and disorders. An emerging area of interest lies in engineering cells to further enhance their innate abilities and confer them with new functionalities. Cellular-based gene therapies is one such example, wherein stem cells are genetically engineered to express therapeutic molecules. Such approaches have shown tremendous potential for cancer applications since stem cells have an innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by the inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Herein, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in mesenchymal stem cells (MSCs). By combining the tumor tropism of the MSCs with the spatiotemporal magnetic nanoparticle-based delivery and activation of TRAIL expression, this platform provides an attractive means with which to enhance our control over the activation of stem cell-based gene therapies. In particular, we found that these engineered cells retained their innate ability to proliferate, differentiate, and, most importantly, home to tumors, making them ideal cellular carriers. Moreover, exposure of the engineered cells to mild hyperthermia, by applying an alternating magnetic field, resulted in the selective expression of TRAIL from the engineered cells. As a result, significant cancer cell death was induced both in vitro and in vivo. Overall, stimuli-responsive stem cell-based gene therapy using multifunctional nanoparticles has immense potential for both cancer and other biomedical applications.