Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H<sub>2</sub>O<sub>2</sub> pathway and alleviating diabetic retinopathy

Si-Yu Gui; Xin-Chen Wang; Zhi-Hao Huang; Mei-Mei Li; Jia-Hao Wang; Si-Yin Gui; Gan-Hua Zhang; Yao Lu; Li-Ming Tao; Hai-Sheng Qian; Zheng-Xuan Jiang

doi:10.1016/j.jpha.2023.05.002

Volume 13 Issue 11

Nov. 2023

Turn off MathJax

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(11): 1326-1345

Si-Yu Gui, Xin-Chen Wang, Zhi-Hao Huang, Mei-Mei Li, Jia-Hao Wang, Si-Yin Gui, Gan-Hua Zhang, Yao Lu, Li-Ming Tao, Hai-Sheng Qian, Zheng-Xuan Jiang. Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1326-1345. doi: 10.1016/j.jpha.2023.05.002

Citation:

Si-Yu Gui, Xin-Chen Wang, Zhi-Hao Huang, Mei-Mei Li, Jia-Hao Wang, Si-Yin Gui, Gan-Hua Zhang, Yao Lu, Li-Ming Tao, Hai-Sheng Qian, Zheng-Xuan Jiang. Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H₂O₂ pathway and alleviating diabetic retinopathy[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1326-1345. doi: 10.1016/j.jpha.2023.05.002

Citation:

Si-Yu Gui, Xin-Chen Wang, Zhi-Hao Huang, Mei-Mei Li, Jia-Hao Wang, Si-Yin Gui, Gan-Hua Zhang, Yao Lu, Li-Ming Tao, Hai-Sheng Qian, Zheng-Xuan Jiang. Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H₂O₂ pathway and alleviating diabetic retinopathy[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1326-1345. doi: 10.1016/j.jpha.2023.05.002

PDF( 8103 KB)

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H₂O₂ pathway and alleviating diabetic retinopathy

doi: 10.1016/j.jpha.2023.05.002

a. Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China;
b. Department of Clinical Medicine, The Second School of Clinical Medicine, Anhui Medical University, Hefei, 230032, China;
c. Department of Clinical Medicine, The First School of Clinical Medicine, Anhui Medical University, Hefei, 230032, China;
d. Department of Laboratory, Fengtai County First People's Hospital, Huainan, Anhui, 232101, China;
e. Department of Immunology, The School of Medicine, Anhui University of Technology, Huainan, Anhui, 232100, China;
f. Department of Nursing, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China;
g. Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China;
h. School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei, 230032, China

Funds:

We thank the Ophthalmology Department of the Second Affiliated Hospital of Anhui Medical University and the Center for Scientific Research of the Second Affiliated Hospital of Anhui Medical University for valuable help in our experiment.

Received Date: Jan. 27, 2023
Accepted Date: May 08, 2023
Rev Recd Date: May 06, 2023
Publish Date: May 12, 2023

Abstract

Abstract

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of vascular cell adhesion molecule-1 (VCAM-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF), causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H₂O₂ signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.
- Nano-coordinated polymer particles,
- Bioactive molecules delivery,
- Antioxidant,
- Anti-angiogenesis,
- Diabetic retinopathy treatment

FullText(HTML)

References(59)

References

GBD 2019 Blindness and Vision Impairment Collaborators, Vision Loss Expert Group of the Global Burden of Disease, Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: The Right to Sight: An analysis for the Global Burden of Disease Study, Lancet Glob. Health 9 (2021) e144-e160.

Z.L. Teo, Y.C. Tham, M. Yu, et al., Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis, Ophthalmology 128 (2021) 1580-1591.

K. Liu, X. Gao, C. Hu, et al., Capsaicin ameliorates diabetic retinopathy by inhibiting poldip2-induced oxidative stress, Redox Biol. 56 (2022), 102460.

X. Tang, J.J. Wang, J. Wang, et al., Endothelium-specific deletion of Nox4 delays retinal vascular development and mitigates pathological angiogenesis, Angiogenesis 24 (2021) 363-377.

Q. Kang, C. Yang, Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications, Redox Biol. 37 (2020), 101799.

Y.-Y. Hua, Y. Zhang, W.-W. Gong, et al., Dihydromyricetin improves endothelial dysfunction in diabetic mice via oxidative stress inhibition in a SIRT3-dependent manner, Int. J. Mol. Sci. 21 (2020), 6699.

L. Liu, X. Yin, X. Wang, et al., Determination of dihydromyricetin in rat plasma by LC-MS/MS and its application to a pharmacokinetic study, Pharm. Biol. 55 (2017) 657-662.

Z. Huang, Y. Wang, D. Yao, et al., Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress, Nat. Commun. 12 (2021), 145.

D. Liu, C. Poon, K. Lu, et al., Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy, Nat. Commun. 5 (2014), 4182.

K.M. Taylor, W.J. Rieter, W. Lin, Manganese-based nanoscale metal-organic frameworks for magnetic resonance imaging, J. Am. Chem. Soc. 130 (2008) 14358-14359.

Y. Peng, P. Liu, Y. Meng, et al., Nanoscale copper(II)-diethyldithiocarbamate coordination polymer as a drug self-delivery system for highly robust and specific cancer therapy, Mol. Pharm. 17 (2020) 2864-2873.

Y. Hu, T. Lv, Y. Ma, et al., Nanoscale coordination polymers for synergistic NO and chemodynamic therapy of liver cancer, Nano Lett. 19 (2019) 2731-2738.

C. He, D. Liu, W. Lin, Self-assembled nanoscale coordination polymers carrying siRNAs and cisplatin for effective treatment of resistant ovarian cancer, Biomaterials 36 (2015) 124-133.

Y. Yu, Z. Huang, Q. Chen, et al., Iron-based nanoscale coordination polymers synergistically induce immunogenic ferroptosis by blocking dihydrofolate reductase for cancer immunotherapy, Biomaterials 288 (2022), 121724.

R. Zhang, B. Xue, Y. Tao, et al., Edge-site engineering of defective Fe-N₄ nanozymes with boosted catalase-like performance for retinal vasculopathies, Adv. Mater. 34 (2022), 2205324.

F. Gong, N. Yang, Y. Wang, et al., Oxygen-deficient bimetallic oxide FeWOX nanosheets as peroxidase-like nanozyme for sensing cancer via photoacoustic Imaging, Small 16 (2020), 2003496.

X. Wang, Z. Yang, Y. Liu, et al., Structural characteristic of polysaccharide isolated from Nostoc commune, and their potential as radical scavenging and antidiabetic activities, Sci. Rep. 12 (2022), 22155.

S. Li, J. Deng, D. Sun, et al., FBXW7 alleviates hyperglycemia-induced endothelial oxidative stress injury via ROS and PARP inhibition, Redox Biol. 58 (2022), 102530.

L.N. Eidson, Q. Gao, H. Qu, et al., Poldip2 controls leukocyte infiltration into the ischemic brain by regulating focal adhesion kinase-mediated VCAM-1 induction, Sci. Rep. 11 (2021), 5533.

D. Zhang, F.L. Lv, G.H. Wang, Effects of HIF-1α on diabetic retinopathy angiogenesis and VEGF expression, Eur. Rev. Med. Pharmacol. Sci. 22 (2018) 5071-5076.

A. Usui-Ouchi, Y. Usui, T. Kurihara, et al., Retinal microglia are critical for subretinal neovascular formation, JCI Insight 5 (2020), e137317.

H.H. Pulkkinen, M. Kiema, J.P. Lappalainen, et al., BMP6/TAZ-Hippo signaling modulates angiogenesis and endothelial cell response to VEGF, Angiogenesis 24 (2021) 129-144.

R. Li, J. Du, Y. Yao, et al., Adiponectin inhibits high glucose-induced angiogenesis via inhibiting autophagy in RF/6A cells, J. Cell. Physiol. 234 (2019) 20566-20576.

L. Le, B. Jiang, W. Wan, et al., Metabolomics reveals the protective of Dihydromyricetin on glucose homeostasis by enhancing insulin sensitivity, Sci. Rep. 6 (2016), 36184.

Y. Zeng, Y.Q. Hua, W. Wang, et al., Modulation of SIRT1-mediated signaling cascades in the liver contributes to the amelioration of nonalcoholic steatohepatitis in high fat fed middle-aged LDL receptor knockout mice by dihydromyricetin, Biochem. Pharmacol. 175 (2020), 113927.

S. Roy, D. Kim, Retinal capillary basement membrane thickening: Role in the pathogenesis of diabetic retinopathy, Prog. Retin. Eye Res. 82 (2021), 100903.

M. Rudraraju, S.P. Narayanan, P.R. Somanath, Regulation of blood-retinal barrier cell-junctions in diabetic retinopathy, Pharmacol. Res. 161 (2020), 105115.

M. Lee, W. Leskova, R.S. Eshaq, et al., Retinal hypoxia and angiogenesis with methamphetamine, Exp. Eye Res. 206 (2021), 108540.

R. Zhang, T. Liu, W. Li, et al., Tumor microenvironment-responsive BSA nanocarriers for combined chemo/chemodynamic cancer therapy, J. Nanobiotechnology 20 (2022), 223.

C. Camaschella, Iron deficiency, Blood 133 (2019) 30-39.

N.J. Kassebaum, GBD 2013 Anemia Collaborators, The global burden of anemia, Hematol. Oncol. Clin. North Am. 30 (2016) 247-308.

Z. Tolkien, L. Stecher, A.P. Mander, et al., Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: A systematic review and meta-analysis, PLoS One 10 (2015), e0117383.

F.M. Hilty, M. Arnold, M. Hilbe, et al., Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation, Nat. Nanotechnol. 5 (2010) 374-380.

K.M. Hosny, Z.M. Banjar, A.H. Hariri, et al., Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia, Drug Des. Devel. Ther. 9 (2015) 313-320.

J. Baumgartner, H.C. Winkler, L. Zandberg, et al., Iron from nanostructured ferric phosphate: Absorption and biodistribution in mice and bioavailability in iron deficient anemic women, Sci. Rep. 12 (2022), 2792.

P. Bonfanti, A. Colombo, M. Saibene, et al., Iron nanoparticle bio-interactions evaluated in Xenopus laevis embryos, a model for studying the safety of ingested nanoparticles, Nanotoxicology 14 (2020) 196-213.

F. Rohner, F.O. Ernst, M. Arnold, et al., Synthesis, characterization, and bioavailability in rats of ferric phosphate nanoparticles, J. Nutr. 137 (2007) 614-619.

S. Chamorro, L. Gutierrez, M.P. Vaquero, et al., Safety assessment of chronic oral exposure to iron oxide nanoparticles, Nanotechnology 26 (2015), 205101.

L.M. von Moos, M. Schneider, F.M. Hilty, et al., Iron phosphate nanoparticles for food fortification: Biological effects in rats and human cell lines, Nanotoxicology 11 (2017) 496-506.

V. Valdiglesias, G. Kilic, C. Costa, et al., Effects of iron oxide nanoparticles: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity, Environ. Mol. Mutagen. 56 (2015) 125-148.

M. Marin-Barba, H. Gavilan, L. Gutierrez, et al., Unravelling the mechanisms that determine the uptake and metabolism of magnetic single and multicore nanoparticles in a Xenopus laevis model, Nanoscale 10 (2018) 690-704.

X. Zhu, S. Tian, Z. Cai, Toxicity assessment of iron oxide nanoparticles in zebrafish (Danio rerio) early life stages, PLoS One 7 (2012), e46286.

R. Gornati, E. Pedretti, F. Rossi, et al., Zerovalent Fe, Co and Ni nanoparticle toxicity evaluated on SKOV-3 and U87 cell lines, J. Appl. Toxicol. 36 (2016) 385-393.

T. Coccini, U. De Simone, M. Roccio, et al., In vitro toxicity screening of magnetite nanoparticles by applying mesenchymal stem cells derived from human umbilical cord lining, J. Appl. Toxicol. 39 (2019) 1320-1336.

F. Cappellini, C. Recordati, M. Maglie, et al., New synthesis and biodistribution of the D-amino acid oxidase-magnetic nanoparticle system, Future Sci. OA 1 (2015), FSO67.

Q. Feng, Y. Liu, J. Huang, et al., Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings, Sci. Rep. 8 (2018), 2082.

K.M. Taylor-Pashow, J. Della Rocca, Z. Xie, et al., Postsynthetic modifications of iron-carboxylate nanoscale metal-organic frameworks for imaging and drug delivery, J. Am. Chem. Soc. 131 (2009) 14261-14263.

Q. Liu, K. Du, M. Liu, et al., Sulfosalicylic acid/Fe³⁺ based nanoscale coordination polymers for effective cancer therapy by the Fenton reaction: An inspiration for understanding the role of aspirin in the prevention of cancer, Biomater. Sci. 7 (2019) 5482-5491.

J. Li, C. Zhang, S. Gong, et al., A nanoscale photothermal agent based on a metal-organic coordination polymer as a drug-loading framework for effective combination therapy, Acta Biomater. 94 (2019) 435-446.

I. Christodoulou, P. Lyu, C.V. Soares, et al., Nanoscale iron-based metal-organic frameworks: Incorporation of functionalized drugs and degradation in biological media, Int. J. Mol. Sci. 24 (2023), 3362.

P. Horcajada, T. Chalati, C. Serre, et al., Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging, Nat. Mater. 9 (2010) 172-178.

C. He, K. Lu, D. Liu, et al., Nanoscale metal-organic frameworks for the co-delivery of cisplatin and pooled siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells, J. Am. Chem. Soc. 136 (2014) 5181-5184.

C. He, D. Liu, W. Lin, Nanomedicine applications of hybrid nanomaterials built from metal-ligand coordination bonds: Nanoscale metal-organic frameworks and nanoscale coordination polymers, Chem. Rev. 115 (2015) 11079-11108.

E. Park, S.W. Chung, ROS-mediated autophagy increases intracellular iron levels and ferroptosis by ferritin and transferrin receptor regulation, Cell Death Dis. 10 (2019), 822.

T.-T. Wei, M.-Y. Zhang, X.-H. Zheng, et al., Interferon-γ induces retinal pigment epithelial cell Ferroptosis by a JAK1-2/STAT1/SLC7A11 signaling pathway in Age-related Macular Degeneration, FEBS J. 289 (2022) 1968-1983.

J. Zhou, P. Hou, Y. Yao, et al., Dihydromyricetin Improves High-Fat Diet-Induced Hyperglycemia through ILC3 Activation via a SIRT3-Dependent Mechanism, Mol. Nutr. Food. Res. 66 (2022), e2101093.

X. Hou, Q. Tong, W. Wang, et al., Dihydromyricetin protects endothelial cells from hydrogen peroxide-induced oxidative stress damage by regulating mitochondrial pathways, Life Sci. 130 (2015) 38-46.

M. Yang, M.G. Tsui, J.K.W. Tsang, et al., Involvement of FSP1-CoQ10-NADH and GSH-GPx-4 pathways in retinal pigment epithelium ferroptosis, Cell Death Dis. 13 (2022), 468.

B.-S. Xie, Y.-Q. Wang, Y. Lin, et al., Inhibition of ferroptosis attenuates tissue damage and improves long-term outcomes after traumatic brain injury in mice, CNS Neurosci. Ther. 25 (2019) 465-475.

Relative Articles

Supplements(0)

Cited By

Proportional views