Science · 2012 · 494 citations · 32 references
PharmacyBioengineeringBiotechnologyBiosensorsDrug DeliveryNanobiotechnologyCancer NanomedicineControlled Release MechanismsMagnetic-responsive Drug DeliveryNanomaterials For Drug DeliveryNanomedicineNanoparticle DesignInsulin BiosynthesisIron Oxide NanoparticlesMagnetic Field-responsive ReleaseMagnetic HyperthermiaMagnetic Nanoparticle Drug DeliveryMagnetic Oxide NanoparticlesProtein ProductionRadio Frequency Wave Heating
Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.
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