Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice

Laboratory of Molecular Genetics, Rockefeller University, New York, NY 10065, USA.
Science (Impact Factor: 33.61). 05/2012; 336(6081):604-8. DOI: 10.1126/science.1216753
Source: PubMed


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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    • "Specifically, they depolarize the membrane by directly changing membrane capacitance rather than by opening the ion channels to which they are ligated. This allows for much faster depolarization than in other strategies where nanoparticle heating leads to opening of temperature-sensitive ion channels (Stanley et al., 2012). The rapid depolarization enabled by the present technique involving membrane capacitance change is critical for temporally precise stimulation of neuronal activity. "
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    • "It has been previously found that specific patterns of cellular calcium oscillation can initiate signaling of gene expression1234. Recently, progresses on optogenetics56789101112, heat-activated promoters13, and gene/protein modification combined with nanoparticles and radio wave14 have successfully demonstrated controllable expression of some genes. However, all those methods include at least three complicated phases: 1) gene or protein engineering/modification, 2) introduction of those bioengineered exogenous materials into cells, and 3) activation of those materials to express corresponding genes by some chemical or physical stimulation. "
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    • "Calcium signalling is rewired to promote calcium-mediated activation of insulin expression. Mice with transplanted tumour xenografts containing this synthetic circuit were exposed to radio waves, which activated the expression and release of insulin from the tumours and, therefore, lowered blood glucose levels in the diabetic mice [35] "
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