A Fluorescent Responsive Hybrid Nanogel for Closed-Loop Control of Glucose

Wu, Weitai; Chen, Shoumin; Hu, Yumei; Zhou, Shuiqin

doi:10.1177/193229681200600421

Cited by 40 publications

(70 citation statements)

References 22 publications

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“…93 A specifically designed hydrogel (zinc oxide poly[N-isopropylacrylamideacrylamide-2-aminomethyl-5-fluorophenylboronic acid]) has been shown to measure glucose levels with high sensitivity and selectivity while simultaneously regulating insulin release in response to glucose values, which may be helpful in making a miniaturized CL. 94 Future studies on overnight CL and predictive low glucose management systems are ongoing.…”

Section: Future Directions In the CL Systemmentioning

confidence: 99%

Closed-Loop System in the Management of Diabetes: Past, Present, and Future

Shah

Shoskes

Tawfik

et al. 2014

Diabetes Technology & Therapeutics

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Intensive insulin therapy (IIT) has been shown to reduce micro- and macrovascular complications in patients with type 1 diabetes mellitus (T1DM). However, IIT is associated with a significant increase in severe hypoglycemic events, resulting in increased morbidity and mortality. Optimization of glycemic control without hypoglycemia (especially nocturnal) should be the next major goal for subjects on insulin treatment. The use of insulin pumps along with continuous glucose monitors (CGMs) has made it easier but requires significant resources and patient education. Research is ongoing to close the loop by integrating the pump and the CGM using different algorithms. The currently available closed-loop system is the threshold suspend. Steps needed to achieve a near-perfect closed-loop are (1) a control-to-range system that will reduce the incidence and/or severity of hyper- and/or hypoglycemia by adjusting the insulin dose and (2) a control-to-target system, a fully automated or hybrid system that sets target glucose levels to individual needs and maintains glucose levels throughout the day using insulin (unihormonal) alone or with other hormones such as glucagon or possibly pramlintide (bihormonal). Future research is also focusing on better insulin delivery devices (pumps), more accurate CGMs, better predictive algorithms, and ultra-rapid-acting insulin analogs to make the closed-loop system as physiological as possible.

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Section: Future Directions In the CL Systemmentioning

confidence: 99%

Closed-Loop System in the Management of Diabetes: Past, Present, and Future

Shah

Shoskes

Tawfik

et al. 2014

Diabetes Technology & Therapeutics

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“…Indeed, we have demonstrated for the first time that optical detection of glucose, glucose response, high yielded insulin loading and storage, and self-regulated insulin delivery could be combined into a multifunctional hybrid nanogel particle, which can be made of fluorescent Ag NPs core covered by a glucose-responsive copolymer gel shell [75]. More recently, we have developed a new class of hybrid nanogels that can integrate glucose sensing and insulin release into a single nano-object [173]. Such a hybrid nanogel is comprised of fluorescent ZnO QDs covalently bonded onto the fluorophenyl boronate derivated nanogel network chains as glucose recognition element, which can sensitively and selectively detect glucose in highly reproducible fluorescent signals over the clinically relevant glucose concentration range of 18-540 mg/dL.…”

Section: Responsive Polymer-inorganic Hybrid Nanogels In Drug Deliverymentioning

confidence: 99%

Responsive Polymer‐Inorganic Hybrid Nanogels for Optical Sensing, Imaging, and Drug Delivery

Wu¹,

Zhou²

2013

Nanomaterials in Drug Delivery, Imaging, and Tissue Engineering

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Responsive hybrid nanogels, comprising inorganic nanoparticles (NPs) immobilized in a polymer nanogel, have recently attracted intensive interest. While inorganic NPs exhibit size-, shape-, and interdistance-dependent optical, magnetic, electronic, and catalytic properties, responsive polymer nanogels can undergo a volume phase transition in response to external stimuli, such as temperature, pH, glucose level, light, and other stimulus, to modify the physicochemical environment of the inorganic NPs immobilized inside. The controllable properties of the responsive hybrid nanogels can offer the possibilities for external switching and manipulation when applied to a diverse range of applications. In this Chapter we provide an analysis of recent advances on the responsive polymer-inorganic hybrid nanogels. The Chapter consists of three major parts: the fundamental theory, synthesis, and applications of the polymer-inorganic hybrid nanogels in optical sensing, diagnostic imaging, and drug delivery.

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“…So far, a variety of optical markers have been explored to prepare the boronic acid-based hybrid nanogels for continuous glucose sensors, including fluorescent organic dyes, semiconductor QDs, and noble metal nanoparticles (NPs). [12][13][14][15][16][17][18][19][20] However, these optical markers have potential problems for practical applications. For example, organic dyes are concerned with poor photostability and potential toxicity, semiconductor QDs are associated with the inherent heavy metal toxicity, and noble metal materials involve high cost.…”

Section: Introductionmentioning

confidence: 98%

“…Consequently, there is widespread research interest in the development of optical continuous glucose sensors based on reversible glucose binding with boronic acids, 4,5 including the polymerized crystalline colloidal array, 6,7 holographic thin films, 8 glucose-mediated assembly of fluorescent dyes and quantum dots (QDs), [9][10][11] and hybrid nanogels embedded with dyes and inorganic nanoparticles. [12][13][14][15][16][17] In particular, the hybrid nanogel-based glucose sensors developed by us have several favorable advantages, including rapid response time, easy engineering on surface, potential biocompatibility, and porous structures for loading insulin and simultaneous glucose-regulated insulin delivery. 16,17 In addition, they can be potentially fabricated into hydrogel-based soft contact lens sensors for glucose detection, which is portable and disposable with no need of electrodes or electric circuits.…”

Section: Introductionmentioning

confidence: 99%

Immobilization of Carbon Dots in Molecularly Imprinted Microgels for Optical Sensing of Glucose at Physiological pH

Wang

Velado

et al. 2015

ACS Appl. Mater. Interfaces

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120

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Nanosized carbon dots (CDs) are emerging as superior fluorophores for biosensing and a bioimaging agent with excellent photostability, chemical inertness, and marginal cytotoxicity. This paper reports a facile one-pot strategy to immobilize the biocompatible and fluorescent CDs (∼6 nm) into the glucose-imprinted poly(N-isopropylacrylamide-acrylamide-vinylphenylboronic acid) [poly(NIPAM-AAm-VPBA)] copolymer microgels for continuous optical glucose detection. The CDs designed with surface hydroxyl/carboxyl groups can form complexes with the AAm comonomers via hydrogen bonds and, thus, can be easily immobilized into the gel network during the polymerization reaction. The resultant glucose-imprinted hybrid microgels can reversibly swell and shrink in response to the variation of surrounding glucose concentration and correspondingly quench and recover the fluorescence signals of the embedded CDs, converting biochemical signals to optical signals. The highly imprinted hybrid microgels demonstrate much higher sensitivity and selectivity for glucose detection than the nonimprinted hybrid microgels over a clinically relevant range of 0-30 mM at physiological pH and benefited from the synergistic effects of the glucose molecular contour and the geometrical constraint of the binding sites dictated by the glucose imprinting process. The highly stable immobilization of CDs in the gel networks provides the hybrid microgels with excellent optical signal reproducibility after five repeated cycles of addition and dialysis removal of glucose in the bathing medium. In addition, the hybrid microgels show no effect on the cell viability in the tested concentration range of 25-100 μg/mL. The glucose-imprinted poly(NIPAM-AAm-VPBA)-CDs hybrid microgels demonstrate a great promise for a new glucose sensor that can continuously monitor glucose level change.

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A Fluorescent Responsive Hybrid Nanogel for Closed-Loop Control of Glucose

Cited by 40 publications

References 22 publications

Closed-Loop System in the Management of Diabetes: Past, Present, and Future

Closed-Loop System in the Management of Diabetes: Past, Present, and Future

Responsive Polymer‐Inorganic Hybrid Nanogels for Optical Sensing, Imaging, and Drug Delivery

Immobilization of Carbon Dots in Molecularly Imprinted Microgels for Optical Sensing of Glucose at Physiological pH

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