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WIREs Nanomed Nanobiotechnol
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Recent advances in nanotechnology for diabetes treatment

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Nanotechnology in diabetes research has facilitated the development of novel glucose measurement and insulin delivery modalities which hold the potential to dramatically improve quality of life for diabetics. Recent progress in the field of diabetes research at its interface with nanotechnology is our focus. In particular, we examine glucose sensors with nanoscale components including metal nanoparticles and carbon nanostructures. The addition of nanoscale components commonly increases glucose sensor sensitivity, temporal response, and can lead to sensors which facilitate continuous in vivo glucose monitoring. Additionally, we survey nanoscale approaches to ‘closed‐loop’ insulin delivery strategies which automatically release insulin in response to fluctuating blood glucose levels (BGLs). ‘Closing the loop’ between BGL measurements and insulin administration by removing the requirement of patient action holds the potential to dramatically improve the health and quality of life of diabetics. Advantages and limitations of current strategies, as well as future opportunities and challenges are also discussed. WIREs Nanomed Nanobiotechnol 2015, 7:548–564. doi: 10.1002/wnan.1329 This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Schematic of the glucose‐responsive nano‐network. (a) Acetal modified dextran nanoparticles containing insulin and GOx. The nanoparticles are coated with positively charged chitosan or negatively charged alginate. (b) Acetal modified dextran molecule. (c) Assembly of oppositely charged nanoparticles to form a nano‐network and insulin release upon the enzymatic generation of gluconic acid under hyperglycemic conditions. (d) Injection of the nano‐network into a STZ‐induced diabetic mouse model. (Reprinted with permission from Ref . Copyright 2013 American Chemical Society)
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Schematic of typical strategies for glucose responsive insulin release. (Reprinted with permission from Ref . Copyright 2014 Chemical Society Reviews)
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In this study, a boronic acid functionalized hydrogel was formed and included suspended silver nanoparticles. The functionalized hydrogel swelled and contracted in proportion to glucose concentration, as a result of the binding interaction between glucose and the boronic acid. As the hydrogel swells, the distance between the Au NPs modulates in response to glucose concentration, and thereby causes a shift in the wavelength of the refracted light. A wavelength shift of 350 nm across the visible spectrum was reported for glucose concentrations ranging from 0 mM to 10 mM. (Reprinted with permission from Ref . Copyright 2014 American Chemical Society)
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In this study, Yum et al. used fluorescent carbon nanotubes with boronic acid to fabricate an optical glucose sensor. As the boronic acid binds to the nanotubes, the fluorescence is quenched. As glucose binds to these boronic acids, the fluorescence returns. Two Boronic acids were found which optimized the desired properties: 4‐cyanophenylboronic and 4‐chlorophenylboronic acid. (Reprinted with permission from Ref . Copyright 2011 American Chemical Society)
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The cobalt nanowires in this image can directly oxidize glucose without the use of enzymes, and thereby generate an amperometric signal proportional to the glucose concentration. An extremely small detection limit was reported (<25 nM), and was attributed to the extremely large surface area of the sensor. This figure depicts scanning electron microscopy images of (a) graphene foam; (b) cobalt nanowires grown on the surface of graphene foam; (c) graphene foam functionalized with cobalt nanowires; (d) high magnification of cobalt nanowires; (E) image of a single cobalt nanowire. (Reprinted with permission from Ref . Copyright 2012 American Chemical Society)
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Yang et al. investigated how nanowires can affect the sensitivity of amperometric glucose sensors. In this experiment, two types of sensors were developed; the first was formed by immobilizing GOx within a bulk hydrogel, and the second was formed by immobilizing GOx on the surface of conductive nanowires. This figure depicts a schematic of the two types of glucose concentration sensors: (a–c) A bulk hydrogel glucose sensor with embedded GOx. (a, d–g) A nanowire glucose sensor with embedded GOx. (h and i) The glucose sensor apparatus. (j and k) The bulk hyrdogel‐GOx sensing system. (i–m) The nanowire‐GOx based glucose sensing system. The nanowire based sensor was more sensitive than the bulk film sensor, which was attributes to its larger surface area, increased GOx loading capacity, and lower electrical resistance. (Reprinted with permission from Ref . Copyright 2014 John Wiley & Sons)
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Glucose‐responsive insulin delivery systems utilizing phenylboronic acid. (a) Insulin release via pH responsive micelles. (b) Multifunctional hydrogel for glucose‐responsive insulin release and glucose concentration measurement. As the smart hydrogel swells in response to hyperglycemic conditions, the insulin is released and the fluorescence of the silver nanoparticles (AgNPs) is modulated. This fluorescence change can be detected and used to quantify the glucose concentration and the release of insulin. (Reprinted with permission from Ref . Copyright 2012 American Chemical Society)
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Schematic of research themes using nanotechnology for diabetes treatment.
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