title: Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice.
abstract: 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.
authors.affiliation: Laboratory of Molecular Genetics, Rockefeller University, New York, NY 10065, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stanley
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Gagner
authors.forename: Shadi
authors.initials: S
authors.lastname: Damanpour
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Yoshida
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Dordick
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Friedman
mesh_terms: D000818:Animals; D057005:Bioengineering; D001786:Blood Glucose / Q000032:analysis*; D002118:Calcium / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000378:metabolism; D000939:Epitopes; D005290:Ferric Compounds; D005293:Ferritins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006358:Hot Temperature; D006801:Humans; D007328:Insulin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D053768:Metal Nanoparticles; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000097:blood / Q000473:pathology; D016716:PC12 Cells; D011846:Radio Waves; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D050916:TRPV Cation Channels / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous
chemical_list: D001786:Blood Glucose; D000939:Epitopes; D005290:Ferric Compounds; D007328:Insulin; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; C000499:ferric oxide; D005293:Ferritins; D002118:Calcium