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      High drug-loading gold nanoclusters for responsive glucose control in type 1 diabetes

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          Abstract

          Background

          Diabetes is one of the biggest medical challenges worldwide. The key to efficiently treat type 1 diabetes is to accurately inject insulin according to the blood glucose levels. In this study, we aimed to develop an intelligent insulin-releasing gold nanocluster system that responds to environmental glucose concentrations.

          Results

          We employed gold nanoclusters (AuNCs) as a novel carrier nanomaterial by taking advantage of their high drug-loading capacity. We prepared AuNCs in the protection of bovine serum albumin, and we decorated AuNCs with 3-aminophenylboronic acid (PBA) as a glucose-responsive factor. Then we grafted insulin onto the surface to obtain the glucose-responsive insulin-releasing system, AuNC-PBA-Ins complex. The AuNC-PBA-Ins complex exhibited high sensitivity to glucose concentration, and rapidly released insulin in high glucose concentration in vitro. In the type 1 diabetic mouse model in vivo, the AuNC-PBA-Ins complex effectively released insulin and regulated blood glucose level in the normoglycemic state for up to 3 days.

          Conclusions

          We successfully developed a phenylboronic acid-functionalized gold nanocluster system (AuNC-PBA-Ins) for responsive insulin release and glucose regulation in type 1 diabetes. This nanocluster system mimics the function of blood glucose regulation of pancreas in the body and may have potential applications in the theranostics of diabetes.

          Electronic supplementary material

          The online version of this article (10.1186/s12951-019-0505-z) contains supplementary material, which is available to authorized users.

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          Most cited references 31

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          Protein-directed synthesis of highly fluorescent gold nanoclusters.

          A simple, one-pot, "green" synthetic route, based on the "biomineralization" capability of a common commercially available protein, bovine serum albumin (BSA), has been developed for the preparation of highly stable Au nanocrystals (NCs) with red emission and high quantum yield.
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            Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides.

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              Effectiveness of sensor-augmented insulin-pump therapy in type 1 diabetes.

              Recently developed technologies for the treatment of type 1 diabetes mellitus include a variety of pumps and pumps with glucose sensors. In this 1-year, multicenter, randomized, controlled trial, we compared the efficacy of sensor-augmented pump therapy (pump therapy) with that of a regimen of multiple daily insulin injections (injection therapy) in 485 patients (329 adults and 156 children) with inadequately controlled type 1 diabetes. Patients received recombinant insulin analogues and were supervised by expert clinical teams. The primary end point was the change from the baseline glycated hemoglobin level. At 1 year, the baseline mean glycated hemoglobin level (8.3% in the two study groups) had decreased to 7.5% in the pump-therapy group, as compared with 8.1% in the injection-therapy group (P<0.001). The proportion of patients who reached the glycated hemoglobin target (<7%) was greater in the pump-therapy group than in the injection-therapy group. The rate of severe hypoglycemia in the pump-therapy group (13.31 cases per 100 person-years) did not differ significantly from that in the injection-therapy group (13.48 per 100 person-years, P=0.58). There was no significant weight gain in either group. In both adults and children with inadequately controlled type 1 diabetes, sensor-augmented pump therapy resulted in significant improvement in glycated hemoglobin levels, as compared with injection therapy. A significantly greater proportion of both adults and children in the pump-therapy group than in the injection-therapy group reached the target glycated hemoglobin level. (Funded by Medtronic and others; ClinicalTrials.gov number, NCT00417989.) 2010 Massachusetts Medical Society
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                Author and article information

                Contributors
                yifenglei@whu.edu.cn
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                3 June 2019
                3 June 2019
                2019
                : 17
                Affiliations
                [1 ]ISNI 0000 0001 2331 6153, GRID grid.49470.3e, School of Power and Mechanical Engineering & The Institute of Technological Sciences, , Wuhan University, ; Wuhan, 430072 China
                [2 ]ISNI 0000 0000 8775 1413, GRID grid.433800.c, School of Material Science and Engineering, , Wuhan Institute of Technology, ; Wuhan, 430205 China
                [3 ]GRID grid.413247.7, Department of Internal Medicine & Geriatrics, , Wuhan University Zhongnan Hospital, ; Wuhan, 430071 China
                Article
                505
                10.1186/s12951-019-0505-z
                6547569
                31159842
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31500775
                Award ID: 81871484
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Biotechnology

                diabetes, glucose-responsive, gold nanoclusters, drug release

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