Skip to main content
SpringerLink
Log in

Aminophenylboronic acid polymer nanoparticles for quantitation of glucose and for insulin release

  • Paper in Forefront
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

We have developed a simple route for the preparation of aminophenylboronic acid polymer nanoparticles (APB PNs) from 3-aminophenylboronic acid and formaldehyde under alkaline conditions according to an extended Stӧber method. Insulin and R6G have been selected to prepare functional insulin-APB PNs and R6G-APB PNs, respectively. During the formation of APB PNs, the representative molecules are embedded inside the APB PNs. Through specific binding of glucose with boronic acid moieties on the R6G-APB PNs and insulin-APB PNs, glucose induces expansion of the APB PNs, leading to release of R6G and insulin molecules, respectively. As a result of release of R6G molecules, the fluorescence intensity of R6G-APB PN solution increases, allowing quantitation of glucose in PBS solutions (10 mM, pH 7.4) with a linear range over 0–10 mM. Release of insulin from insulin-APB PNs is significant and rapid when the glucose concentration is higher than 7 mM. Having advantages of low cost, simple preparation, biocompatibility, and continuous response to glucose, the insulin-APB PNs hold great potential as an alternative for treating diabetic patients.

Quantitation of glucose and release of insulin by glucose responsive 3-aminophenylboronic acid polymer nanoparticles

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Shan C, Yang H, Song J, Han D, Ivaska A, Niu L. Direct electrochemistry of glucose oxidase and biosensing for glucose based on graphene. Anal Chem. 2009;81(6):2378–82.

    Article  CAS  Google Scholar 

  2. Yeh TY, Wang CI, Chang HT. Photoluminescent C-dots@RGO for sensitive detection of hydrogen peroxide and glucose. Talanta. 2013;115:718–23.

    Article  CAS  Google Scholar 

  3. Timko BP, Arruebo M, Shankarappa SA, McAlvin JB, Okonkwo OS, Mizrahi B, et al. Near-infrared-actuated devices for remotely controlled drug delivery. Proc Natl Acad Sci U S A. 2014;111(4):1349–54.

    Article  CAS  Google Scholar 

  4. Ma R, Shi L. Phenylboronic acid-based glucose-responsive polymeric nanoparticles: synthesis and applications in drug delivery. Polym Chem. 2014;5(5):1503–18.

    Article  CAS  Google Scholar 

  5. Horgan AM, Marshall AJ, Kew SJ, Dean KES, Creasey CD, Kabilan S. Crosslinking of phenylboronic acid receptors as a means of glucose selective holographic detection. Biosens Bioelectron. 2006;21(9):1838–45.

    Article  CAS  Google Scholar 

  6. Zenkl G, Mayr T, Klimant I. Sugar-responsive fluorescent nanospheres. Macromol Biosci. 2008;8(2):146–52.

    Article  CAS  Google Scholar 

  7. Lorand JP, Edwards JO. Polyol complexes and structure of the benzeneboronate ion. J Org Chem. 1959;24(6):769–74.

    Article  CAS  Google Scholar 

  8. Springsteen G, Wang B. A detailed examination of boronic acid–diol complexation. Tetrahedron. 2002;58(26):5291–300.

    Article  CAS  Google Scholar 

  9. Farooqi ZH, Wu W, Zhou S, Siddiq M. Engineering of phenylboronic acid based glucose-sensitive microgels with 4-vinylpyridine for working at physiological pH and temperature. Macromol Chem Phys. 2011;212(14):1510–4.

    Article  CAS  Google Scholar 

  10. Zhao L, Xiao C, Ding J, He P, Tang Z, Pang X, et al. Facile one-pot synthesis of glucose-sensitive nanogel via thiol-ene click chemistry for self-regulated drug delivery. Acta Biomater. 2013;9(5):6535–43.

    Article  CAS  Google Scholar 

  11. Liu J, Qiao SZ, Liu H, Chen J, Orpe A, Zhao D, et al. Extension of the Stöber method to the preparation of monodisperse resorcinol-formaldehyde resin polymer and carbon spheres. Angew Chem Int Ed. 2011;50(26):5947–051.

    Article  CAS  Google Scholar 

  12. Zhao J, Niu W, Zhang L, Cai H, Han M, Yuan Y, et al. A template-free and surfactant-free method for high-yield synthesis of highly monodisperse 3-aminophenol-formaldehyde resin and carbon nano/microspheres. Macromolecules. 2013;46(1):140–5.

    Article  CAS  Google Scholar 

  13. Ho LC, Hsu CH, Ou CM, Wang CW, Liu TP, Hwang LP, et al. Unibody core-shell smart polymer as a theranostic nanoparticle for drug delivery and MR imaging. Biomaterials. 2015;37:436–46.

    Article  CAS  Google Scholar 

  14. Ho LC, Ou CM, Li CL, Chen SY, Li HW, Chang HT. Sensitive pH probes of retro-self-quenching fluorescent nanoparticles. J Mater Chem B. 2013;1(18):2425–32.

    Article  CAS  Google Scholar 

  15. Zhuang X, Ha T, Kim HD, Centner T, Labeit S, Chu S. Fluorescence quenching: a tool for single-molecule protein-folding study. Proc Natl Acad Sci U S A. 2000;97(26):14241–4.

    Article  CAS  Google Scholar 

  16. Carru C, Zinellu A, Sotgia S, Serra R, Usai MF, Pintus GF, et al. A new HPLC method for serum neopterin measurement and relationships with plasma thiols levels in healthy subjects. Biomed Chromatogr. 2004;18(6):360–6.

    Article  CAS  Google Scholar 

  17. Kawasaki T, Ogata N, Akanuma H, Sakai T, Watanabe H, Ichiyanagi K, et al. Postprandial plasma fructose level is associated with retinopathy in patients with type 2 diabetes. Metabolism. 2004;53(5):583–688.

    Article  CAS  Google Scholar 

  18. Taguchi T, Miwa I, Mizutani T, Nakajima H, Fukumura Y, Kobayashi I, et al. Determination of d-mannose in plasma by HPLC. Clin Chem. 2003;49(1):181–3.

    Article  CAS  Google Scholar 

  19. Zor T, Selinger Z. Linearization of the Bradford protein assay increases its sensitivity: theoretical and experimental studies. Anal Biochem. 1996;236(2):302–8.

    Article  CAS  Google Scholar 

  20. Turner RC, Holman RR, Cull CA, Stratton IM, Matthews DR, Fright V, et al. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352(9131):837–53.

    Article  Google Scholar 

  21. James TD, Phillips MD, Shinkai S. Boronic acids in saccharide recognition. 1st ed. Cambridge: The Royal Society of Chemistry; 2006.

    Google Scholar 

  22. Ho LC, Wu WC, Chang CY, Hsieh HH, Lee CH, Chang HT. Aptamer-conjugated polymeric nanoparticles for the detection of cancer cells through “turn-on” retro-self-quenched fluorescence. Anal Chem. 2015;87(9):4925–32.

    Article  CAS  Google Scholar 

  23. Zhang Y, Guan Y, Zhou S. Synthesis and volume phase transitions of glucose-sensitive microgels. Biomacromolecules. 2006;7(11):3196–201.

    Article  CAS  Google Scholar 

  24. Savsunenko O, Matondo H, Franceschi-Messant S, Perez E, Popov AF, Rico-Lattes I, et al. Functionalized vesicles based on amphiphilic boronic acids: a system for recognizing biologically important polyols. Langmuir. 2013;29(10):3207–13.

    Article  CAS  Google Scholar 

  25. Yang H, Sun X, Liu G, Ma R, Li Z, An Y, et al. Glucose-responsive complex micelles for self-regulated release of insulin under physiological conditions. Soft Matter. 2013;9(35):8589–99.

    Article  CAS  Google Scholar 

  26. Angyal SJ. The composition of reducing sugars in solution. Adv Carbohydr Chem Biochem. 1984;42:15–68.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the Ministry of Science and Technology (MOST) of Taiwan for providing financial support for this study under contracts NSC 104-2113-M-002-008-MY3 and 104-2815-C-002-118-M. The authors thank Chia-Chuan Cho and Professor Hung-Wen Li from the Department of Chemistry, National Taiwan University, for their help with fluorescence microscopy. Also, the assistances of Ms. Ya-Yun Yang and Ms. Ching-Yen Lin from the Instrument Center of National Taiwan University (NTU) for TEM measurement is appreciated.

Author information

Authors and Affiliations

  1. Department of Chemistry, National Taiwan University, 1, Section 4, Roosevelt Road, Taipei, 10617, Taiwan

    Hao-Hsuan Hsieh, Lin-Chen Ho & Huan-Tsung Chang

Authors
  1. Hao-Hsuan Hsieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin-Chen Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huan-Tsung Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Huan-Tsung Chang.

Ethics declarations

All volunteer blood donors who are from this lab have given written informed consent for use of their samples. The experiments were conducted in accordance with ethical standards.

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(PDF 616 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hsieh, HH., Ho, LC. & Chang, HT. Aminophenylboronic acid polymer nanoparticles for quantitation of glucose and for insulin release. Anal Bioanal Chem 408, 6557–6565 (2016). https://doi.org/10.1007/s00216-016-9842-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-016-9842-z

Keywords

Search

Navigation