Selenium Nanodots (SENDs) As Antioxidants and Antioxidant-Prodrugs to Rescue Islet β Cells in Type 2 Diabetes Mellitus by Restoring Mitophagy and Alleviating Endoplasmic Reticulum Stress

Overview

Journal Adv Sci (Weinh)

Specialty Biomedical Engineering

Date 2023 Jul 6

PMID 37408520

Authors

Qiong Huang

Zerun Liu

Yunrong Yang

Yuqi Yang

Ting Huang

Ying Hong

Jinping Zhang

Qiaohui Chen

Tianjiao Zhao

Zuoxiu Xiao

Xuejun Gong

Yitian Jiang

Jiang Peng

Yayun Nan

Kelong Ai

Affiliations

Soon will be listed here.

Abstract

Preventing islet β-cells death is crucial for treating type 2 diabetes mellitus (T2DM). Currently, clinical drugs are being developed to improve the quality of T2DM care and self-care, but drugs focused on reducing islets β-cell death are lacking. Given that β-cell death in T2DM is dominated ultimately by excessive reactive oxygen species (ROS), eliminating excessive ROS in β-cells is a highly promising therapeutic strategy. Nevertheless, no antioxidants have been approved for T2DM therapy because most of them cannot meet the long-term and stable elimination of ROS in β-cells without eliciting toxic side-effects. Here, it is proposed to restore the endogenous antioxidant capacity of β-cells to efficiently prevent β-cell death using selenium nanodots (SENDs), a prodrug of the antioxidant enzyme glutathione peroxidase 1 (GPX1). SENDs not only scavenge ROS effectively, but also "send" selenium precisely to β-cells with ROS response to greatly enhance the antioxidant capacity of β-cells by increasing GPX1 expression. Therefore, SENDs greatly rescue β-cells by restoring mitophagy and alleviating endoplasmic reticulum stress (ERS), and demonstrate much stronger efficacy than the first-line drug metformin for T2DM treatment. Overall, this strategy highlights the great clinical application prospects of SENDs, offering a paradigm for an antioxidant enzyme prodrug for T2DM treatment.

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References

Sies H, Jones D . Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020; 21(7):363-383. DOI: 10.1038/s41580-020-0230-3. View

Wang X, Vatamaniuk M, Wang S, Roneker C, Simmons R, Lei X . Molecular mechanisms for hyperinsulinaemia induced by overproduction of selenium-dependent glutathione peroxidase-1 in mice. Diabetologia. 2008; 51(8):1515-24. DOI: 10.1007/s00125-008-1055-3. View

Perreault L, Skyler J, Rosenstock J . Novel therapies with precision mechanisms for type 2 diabetes mellitus. Nat Rev Endocrinol. 2021; 17(6):364-377. DOI: 10.1038/s41574-021-00489-y. View

Kerry R, Mahapatra G, Maurya G, Patra S, Mahari S, Das G . Molecular prospect of type-2 diabetes: Nanotechnology based diagnostics and therapeutic intervention. Rev Endocr Metab Disord. 2020; 22(2):421-451. DOI: 10.1007/s11154-020-09606-0. View

Poitout V, Robertson R . Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev. 2007; 29(3):351-66. PMC: 2528858. DOI: 10.1210/er.2007-0023. View

Acosta-Montano P, Rodriguez-Velazquez E, Ibarra-Lopez E, Frayde-Gomez H, Mas-Oliva J, Delgado-Coello B . Fatty Acid and Lipopolysaccharide Effect on Beta Cells Proteostasis and its Impact on Insulin Secretion. Cells. 2019; 8(8). PMC: 6721695. DOI: 10.3390/cells8080884. View

Liu M, Huang Y, Xu X, Li X, Alam M, Arunagiri A . Normal and defective pathways in biogenesis and maintenance of the insulin storage pool. J Clin Invest. 2021; 131(2). PMC: 7810482. DOI: 10.1172/JCI142240. View

Vercellino I, Sazanov L . The assembly, regulation and function of the mitochondrial respiratory chain. Nat Rev Mol Cell Biol. 2021; 23(2):141-161. DOI: 10.1038/s41580-021-00415-0. View

Yang C, Eleftheriadou M, Kelaini S, Morrison T, Vila Gonzalez M, Caines R . Targeting QKI-7 in vivo restores endothelial cell function in diabetes. Nat Commun. 2020; 11(1):3812. PMC: 7393072. DOI: 10.1038/s41467-020-17468-y. View

10.

Donath M, Dinarello C, Mandrup-Poulsen T . Targeting innate immune mediators in type 1 and type 2 diabetes. Nat Rev Immunol. 2019; 19(12):734-746. DOI: 10.1038/s41577-019-0213-9. View

11.

Zhao J, Zou H, Huo Y, Wei X, Li Y . Emerging roles of selenium on metabolism and type 2 diabetes. Front Nutr. 2022; 9:1027629. PMC: 9686347. DOI: 10.3389/fnut.2022.1027629. View

12.

Mohamed A, Khater S, Arisha A, Metwally M, Mostafa-Hedeab G, El-Shetry E . Chitosan-stabilized selenium nanoparticles alleviate cardio-hepatic damage in type 2 diabetes mellitus model via regulation of caspase, Bax/Bcl-2, and Fas/FasL-pathway. Gene. 2020; 768:145288. DOI: 10.1016/j.gene.2020.145288. View

13.

Forman H, Zhang H . Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 2021; 20(9):689-709. PMC: 8243062. DOI: 10.1038/s41573-021-00233-1. View

14.

Zhu Y, Liu Q, Zhou Z, Ikeda Y . PDX1, Neurogenin-3, and MAFA: critical transcription regulators for beta cell development and regeneration. Stem Cell Res Ther. 2017; 8(1):240. PMC: 5667467. DOI: 10.1186/s13287-017-0694-z. View

15.

Brown O, Bridge K, Kearney M . Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Glucose Homeostasis and Diabetes-Related Endothelial Cell Dysfunction. Cells. 2021; 10(9). PMC: 8469180. DOI: 10.3390/cells10092315. View

16.

Chen Q, Nan Y, Yang Y, Xiao Z, Liu M, Huang J . Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney. Bioact Mater. 2022; 22:141-167. PMC: 9526023. DOI: 10.1016/j.bioactmat.2022.09.021. View

17.

Huang Q, Yang Y, Zhu Y, Chen Q, Zhao T, Xiao Z . Oral Metal-Free Melanin Nanozymes for Natural and Durable Targeted Treatment of Inflammatory Bowel Disease (IBD). Small. 2023; 19(19):e2207350. DOI: 10.1002/smll.202207350. View

18.

Steinbrenner H, Duntas L, Rayman M . The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities. Redox Biol. 2022; 50:102236. PMC: 8844812. DOI: 10.1016/j.redox.2022.102236. View

19.

Quizon M, Garcia A . Engineering β Cell Replacement Therapies for Type 1 Diabetes: Biomaterial Advances and Considerations for Macroscale Constructs. Annu Rev Pathol. 2021; 17:485-513. DOI: 10.1146/annurev-pathol-042320-094846. View

20.

Llanos P, Contreras-Ferrat A, Barrientos G, Valencia M, Mears D, Hidalgo C . Glucose-Dependent Insulin Secretion in Pancreatic β-Cell Islets from Male Rats Requires Ca2+ Release via ROS-Stimulated Ryanodine Receptors. PLoS One. 2015; 10(6):e0129238. PMC: 4457734. DOI: 10.1371/journal.pone.0129238. View