Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy
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 spec...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Journal of Pharmaceutical Analysis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177923000904 |
| _version_ | 1797398609861279744 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Si-Yu Gui |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T01:28:02Z |
| format | Article |
| id | doaj.art-15b85f5e5f3f42dd9f69ed8b05af8c86 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-03-09T01:28:02Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-15b85f5e5f3f42dd9f69ed8b05af8c862023-12-10T06:14:40ZengElsevierJournal of Pharmaceutical Analysis2095-17792023-11-01131113261345Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathySi-Yu Gui0Xin-Chen Wang1Zhi-Hao Huang2Mei-Mei Li3Jia-Hao Wang4Si-Yin Gui5Gan-Hua Zhang6Yao Lu7Li-Ming Tao8Hai-Sheng Qian9Zheng-Xuan Jiang10Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Department of Clinical Medicine, The Second School of Clinical Medicine, Anhui Medical University, Hefei, 230032, ChinaDepartment of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Department of Clinical Medicine, The Second School of Clinical Medicine, Anhui Medical University, Hefei, 230032, ChinaDepartment of Clinical Medicine, The Second School of Clinical Medicine, Anhui Medical University, Hefei, 230032, ChinaDepartment of Clinical Medicine, The First School of Clinical Medicine, Anhui Medical University, Hefei, 230032, ChinaDepartment of Clinical Medicine, The First School of Clinical Medicine, Anhui Medical University, Hefei, 230032, ChinaDepartment of Laboratory, Fengtai County First People's Hospital, Huainan, Anhui, 232101, China; Department of Immunology, The School of Medicine, Anhui University of Technology, Huainan, Anhui, 232100, ChinaDepartment of Nursing, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China; Corresponding author.Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Corresponding author.School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei, 230032, China; Corresponding author.Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2095177923000904Nano-coordinated polymer particlesBioactive molecules deliveryAntioxidantAnti-angiogenesisDiabetic retinopathy treatment |
| spellingShingle | 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 Journal of Pharmaceutical Analysis Nano-coordinated polymer particles Bioactive molecules delivery Antioxidant Anti-angiogenesis Diabetic retinopathy treatment |
| title | Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy |
| title_full | Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy |
| title_fullStr | Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy |
| title_full_unstemmed | Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy |
| title_short | Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy |
| title_sort | nanoscale coordination polymer fe dmy downregulating poldip2 nox4 h2o2 pathway and alleviating diabetic retinopathy |
| topic | Nano-coordinated polymer particles Bioactive molecules delivery Antioxidant Anti-angiogenesis Diabetic retinopathy treatment |
| url | http://www.sciencedirect.com/science/article/pii/S2095177923000904 |
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