Journal Home > Volume 15 , Issue 6
Nano Research 2022, 15(6): 5205-5215 https://doi.org/10.1007/s12274-022-4105-0
Research Article | Issue | Published: 04 March 2022

Glucose-responsive erythrocyte-bound nanoparticles for continuously modulated insulin release

Show Author's Information Xiaomin Xu1,  Yani Xu1,  Yuai Li1,  Min Li1,  Leilei Wang1,  Qiang Zhang1,  Bingjie Zhou1,  Qing Lin1,  Tao Gong1,  Xun Sun1,  Zhirong Zhang1( ),  Ling Zhang2( )
Key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China
Keywords:
diabetes, glucose-responsive, erythrocyte-biomimetic, insulin release, blood glucose control
Topics:
Nano biology
Cite this article:
Xu X, Xu Y, Li Y, et al. Glucose-responsive erythrocyte-bound nanoparticles for continuously modulated insulin release. Nano Research, 2022, 15(6): 5205-5215. https://doi.org/10.1007/s12274-022-4105-0
Download citation
EndNote(RIS)
BibTeX

888

Views

49

Downloads

Citations

5

Crossref

4

WoS

4

Scopus

0

CSCD

Abstract Full text Electronic supplementary material About this article

Glucose-responsive closed-loop insulin delivery systems represent a promising treatment strategy for diabetes, but current systems generally cannot achieve long-term effects. In this study, we designed an erythrocyte-biomimetic glucose-responsive system (EGRS) by coupling glucose-responsive nanoparticles (GRNs) to red blood cells; these nanoparticles exhibited the dual functions of glucose-responsiveness and persistent presence in circulation. GRNs are generated by encapsulating with insulin through ion crosslinking, followed by coloading with glucose oxidase (GOx) and catalase (CAT), a process that endows the nanoparticles with glucose-responsiveness. Simultaneously, the GRNs are coupled with red blood cells to camouflage them from the immune system, therefore, these erythrocyte-coupled GRNs can circulate in the blood for a long time. Under conditions of hyperglycemia, GOx acts on blood glucose to produce gluconic acid, which causes the rupture of GRNs and efficient release of insulin. Conversely, insulin is only released at the basic rate during hypoglycemia. Thus, EGRS can efficiently and continuously respond to hyperglycemia to maintain blood glucose levels within the normal range.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Glucose-responsive erythrocyte-bound nanoparticles for continuously modulated insulin release

Show Author's information Xiaomin Xu1, Yani Xu1, Yuai Li1, Min Li1, Leilei Wang1, Qiang Zhang1, Bingjie Zhou1, Qing Lin1, Tao Gong1, Xun Sun1, Zhirong Zhang1( ), Ling Zhang2( )
Key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, China

Abstract

Glucose-responsive closed-loop insulin delivery systems represent a promising treatment strategy for diabetes, but current systems generally cannot achieve long-term effects. In this study, we designed an erythrocyte-biomimetic glucose-responsive system (EGRS) by coupling glucose-responsive nanoparticles (GRNs) to red blood cells; these nanoparticles exhibited the dual functions of glucose-responsiveness and persistent presence in circulation. GRNs are generated by encapsulating with insulin through ion crosslinking, followed by coloading with glucose oxidase (GOx) and catalase (CAT), a process that endows the nanoparticles with glucose-responsiveness. Simultaneously, the GRNs are coupled with red blood cells to camouflage them from the immune system, therefore, these erythrocyte-coupled GRNs can circulate in the blood for a long time. Under conditions of hyperglycemia, GOx acts on blood glucose to produce gluconic acid, which causes the rupture of GRNs and efficient release of insulin. Conversely, insulin is only released at the basic rate during hypoglycemia. Thus, EGRS can efficiently and continuously respond to hyperglycemia to maintain blood glucose levels within the normal range.

Keywords: diabetes, glucose-responsive, erythrocyte-biomimetic, insulin release, blood glucose control

References(35)

1

Alberti, K. G. M. M.; Zimmet, P. Z. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet. Med. 1998, 15, 539–553.
DOI
2

Saeedi, P.; Petersohn, I.; Salpea, P.; Malanda, B.; Karuranga, S.; Unwin, N.; Colagiuri, S.; Guariguata, L.; Motala, A. A.; Ogurtsova, K. et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the international diabetes federation diabetes atlas, 9th edition. Diabetes Res. Clin. Pract. 2019, 157, 107843.
DOI Google Scholar
3

Laakso, M. Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 1999, 48, 937–942.
DOI Google Scholar
4

Garyu, J. W.; Meffre, E.; Cotsapas, C.; Herold, K. C. Progress and challenges for treating Type 1 diabetes. J. Autoimmun. 2016, 71, 1–9.
DOI Google Scholar
5

Wang, J. Q.; Wang, Z. J.; Yu, J. C.; Kahkoska, A. R.; Buse, J. B.; Gu, Z. Glucose-responsive insulin and delivery systems: Innovation and translation. Adv. Mater. 2020, 32, 1902004.
DOI Google Scholar
6

Yu, J. C.; Zhang, Y. Q.; Yan, J. J.; Kahkoska, A. R.; Gu, Z. Advances in bioresponsive closed-loop drug delivery systems. Int. J. Pharm. 2018, 544, 350–357.
DOI Google Scholar
7

Bratlie, K. M.; York, R. L.; Invernale, M. A.; Langer, R.; Anderson, D. G. Materials for diabetes therapeutics. Adv. Healthc. Mater. 2012, 1, 267–284.
DOI Google Scholar
8

Wilson, R.; Turner, A. P. F. Glucose oxidase: An ideal enzyme. Biosens. Bioelectron. 1992, 7, 165–185.
DOI Google Scholar
9

Huggett, A. S. G.; Nixon, D. A. Use of glucose oxidase, peroxidase, and O-dianisidine in determination of blood and urinary glucose. Lancet 1957, 270, 368–370.
DOI Google Scholar
10

Bankar, S. B.; Bule, M. V.; Singhal, R. S.; Ananthanarayan, L. Glucose oxidase—an overview. Biotechnol. Adv. 2009, 27, 489–501.
DOI Google Scholar
11

Luo, F. Q.; Chen, G. J.; Xu, W.; Zhou, D. J.; Li, J. X.; Huang, Y. C.; Lin, R.; Gu, Z.; Du, J. Z. Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery. Nano Res. 2021, 14, 2689–2696.
DOI Google Scholar
12

Qi, W.; Yan, X. H.; Fei, J. B.; Wang, A. H.; Cui, Y.; Li, J. B. Triggered release of insulin from glucose-sensitive enzyme multilayer shells. Biomaterials 2009, 30, 2799–2806.
DOI Google Scholar
13

Yu, J. C.; Zhang, Y. Q.; Wang, J. Q.; Wen, D.; Kahkoska, A. R.; Buse, J. B.; Gu, Z. Glucose-responsive oral insulin delivery for postprandial glycemic regulation. Nano Res. 2019, 12, 1539–1545.
DOI Google Scholar
14

Fu, Y.; Liu, W.; Wang, L. Y.; Zhu, B. Y.; Qu, M. K.; Yang, L. Q.; Sun, X.; Gong, T.; Zhang, Z. R.; Lin, Q. et al. Erythrocyte-membrane-camouflaged nanoplatform for intravenous glucose-responsive insulin delivery. Ad. Funct. Mater. 2018, 28, 1802250.
DOI Google Scholar
15

Biagiotti, S.; Paoletti, M. F.; Fraternale, A.; Rossi, L.; Magnani, M. Drug delivery by red blood cells. IUBMB Life 2011, 63, 621–631.
DOI Google Scholar
16

Bush, L. M.; Healy, C. P.; Javdan, S. B.; Emmons, J. C.; Deans, T. L. Biological cells as therapeutic delivery vehicles. Trends Pharmacol. Sci. 2021, 42, 106–118.
DOI Google Scholar
17

Suk, J. S.; Xu, Q. G.; Kim, N.; Hanes, J.; Ensign, L. M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 2016, 99, 28–51.
DOI Google Scholar
18

Chambers, E.; Mitragotri, S. Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. J. Control. Release 2004, 100, 111–119.
DOI Google Scholar
19

Xia, D. L.; He, H.; Wang, Y.; Wang, K. Y.; Zuo, H. Q.; Gu, H. Y.; Xu, P. P.; Hu, Y. Ultrafast glucose-responsive, high loading capacity erythrocyte to self-regulate the release of insulin. Acta Biomater. 2018, 69, 301–312.
DOI Google Scholar
20

Wang, C.; Ye, Y. Q.; Sun, W. J.; Yu, J. C.; Wang, J. Q.; Lawrence, D. S.; Buse, J. B.; Gu, Z. Red blood cells for glucose-responsive insulin delivery. Adv. Mater. 2017, 29, 1606617.
DOI Google Scholar
21

Wang, Y. L.; Khan, A.; Liu, Y. X.; Feng, J.; Dai, L.; Wang, G. H.; Alam, N.; Tong, L.; Ni, Y. H. Chitosan oligosaccharide-based dual pH responsive nano-micelles for targeted delivery of hydrophobic drugs. Carbohydr. Polym. 2019, 223, 115061.
DOI Google Scholar
22

Motiei, M.; Sedlařík, V.; Lucia, L. A.; Fei, H. J.; Münster, L. Stabilization of chitosan-based polyelectrolyte nanoparticle cargo delivery biomaterials by a multiple ionic cross-linking strategy. Carbohydr. Polym. 2020, 231, 115709.
DOI Google Scholar
23

Yao, H.; Wynendaele, E.; Xu, X. L.; Kosgei, A.; De Spiegeleer, B. Circular dichroism in functional quality evaluation of medicines. J. Pharm. Biomed. Anal. 2018, 147, 50–64.
DOI Google Scholar
24

Di, J. W.; Gao, X.; Du, Y. M.; Zhang, H.; Gao, J.; Zheng, A. P. Size, shape, charge and “stealthy” surface: Carrier properties affect the drug circulation time in vivo. Asian J. Pharm. Sci. 2021, 16, 444–458.
DOI Google Scholar
25

Poon, W.; Zhang, Y. N.; Ouyang, B.; Kingston, B. R.; Wu, J. L. Y.; Wilhelm, S.; Chan, W. C. W. Elimination pathways of nanoparticles. ACS Nano 2019, 13, 5785–5798.
DOI Google Scholar
26

Andrikopoulos, S.; Blair, A. R.; Deluca, N.; Fam, B. C.; Proietto, J. Evaluating the glucose tolerance test in mice. Am. J. Physiol. Endocrinol. Metab. 2008, 295, E1323–E1332.
DOI Google Scholar
27

Paes, T.; Rolim, L. C.; Filho, C. S.; De Sa, J. R.; Dib, S. A. Awareness of hypoglycemia and spectral analysis of heart rate variability in type 1 diabetes. J. Diabetes Complications 2020, 34, 107617.
DOI Google Scholar
28

Chetan, M. R.; Thrower, S. L.; Narendran, P. What is type 1 diabetes? Medicine 2019, 47, 5–9.
DOI Google Scholar
29

Berenson, D. F.; Weiss, A. R.; Wan, Z. L.; Weiss, M. A. Insulin analogs for the treatment of diabetes mellitus: Therapeutic applications of protein engineering. Ann. NY Acad. Sci. 2011, 1243, E40–E54.
DOI Google Scholar
30

Tékus, V.; Horváth, Á. I.; Csekő, K.; Szabadfi, K.; Kovács-Valasek, A.; Dányádi, B.; Deres, L.; Halmosi, R.; Sághy, É.; Varga, Z. V. et al. Protective effects of the novel amine-oxidase inhibitor multi-target drug SZV 1287 on streptozotocin-induced beta cell damage and diabetic complications in rats. Biomed. Pharmacother. 2021, 134, 111105.
DOI Google Scholar
31

Raghav, A.; Ahmad, J. Glycated serum albumin: A potential disease marker and an intermediate index of diabetes control. Diabetes Metab. Syndr. :Clin. Res. Rev. 2014, 8, 245–251.
DOI Google Scholar
32

Giri, B.; Dey, S.; Das, T.; Sarkar, M.; Banerjee, J.; Dash, S. K. Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity. Biomed. Pharmacother. 2018, 107, 306–328.
DOI Google Scholar
33

Shawahna, R.; Shanti, Y.; Al Zabadi, H.; Sharabati, M.; Alawneh, A.; Shaqu, R.; Taha, I.; Bustami, A. Prevalence and association of clinical characteristics and biochemical factors with complications of diabetes mellitus in Palestinians treated in primary healthcare practice. Diabetes Metab. Syndr. :Clin. Res. Rev. 2018, 12, 693–704.
DOI Google Scholar
34

Jayapandian, C. P.; Chen, Y. J.; Janowczyk, A. R.; Palmer, M. B.; Cassol, C. A.; Sekulic, M.; Hodgin, J. B.; Zee, J.; Hewitt, S. M.; O’Toole, J. et al. Development and evaluation of deep learning-based segmentation of histologic structures in the kidney cortex with multiple histologic stains. Kidney Int. 2021, 99, 86–101.
DOI Google Scholar
35

Mitra, M. S.; DeMarco, S.; Holub, B.; Thiruneelakantapillai, L.; Thackaberry, E. A. Development of peptide therapeutics: A nonclinical safety assessment perspective. Regul. Toxicol. Pharmacol. 2020, 117, 104766.
DOI Google Scholar
File
12274_2022_4105_MOESM1_ESM.pdf (1.2 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 25 October 2021
Revised: 20 December 2021
Accepted: 22 December 2021
Published: 04 March 2022
Issue date: June 2022

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported by the Regional Innovation and Development Joint Fund (No. U20A20411), the National Science Fund for Excellent Young Scholars (No. 82022070).

The animal study protocol was approved by the Institutional Animal Care and Ethics Committee of Sichuan University (No. SYXK2013-113).

Return