Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization
Background. Pathological neovascularization, which involves a disruption in the balance between angiogenic and antiangiogenic factors under pathological conditions, is the basis of many intraocular diseases. Pigment epithelium-derived factor (PEDF) is a potent natural, endogenous inhibitor of neovas...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2022/1193760 |
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| author | Feng Zhao Wenlei Fei Zhouyue Li Hanyang Yu Lei Xi |
| author_facet | Feng Zhao Wenlei Fei Zhouyue Li Hanyang Yu Lei Xi |
| author_sort | Feng Zhao |
| collection | DOAJ |
| description | Background. Pathological neovascularization, which involves a disruption in the balance between angiogenic and antiangiogenic factors under pathological conditions, is the basis of many intraocular diseases. Pigment epithelium-derived factor (PEDF) is a potent natural, endogenous inhibitor of neovascularization because of its antiangiogenic and neuroprotective benefits. However, its application is restricted by its instability and short half-life. The present study is aimed at investigating the cytotoxicity and antiangiogenic effects of PEDF-loaded PEGylated nanoparticles (NP-PEG-PEDF) on high glucose-stimulated human umbilical vein endothelial cells (HUVECs). Methods. In this study, NP-PEG-PEDF were fabricated using the multiple emulsion method for the first time. HUVECs were cultured in a high concentration of glucose (30 mmol/L D-glucose), simulating diabetic conditions. The antiangiogenic effects of vascular endothelial growth factor (VEGF), pure PEDF, and NP-PEG-PEDF on proliferation, migration, and tube formation were evaluated. VEGF secretion in high glucose-stimulated HUVECs was further tested in vitro. Results. NP-PEG-PEDF exhibited low cytotoxicity in HUVECs. Our results indicated that in vitro, NP-PEG-PEDF attenuated diabetes-induced HUVEC proliferation, migration, and tube formation and suppressed VEGF secretion. The apoptosis of diabetes-induced HUVECs occurred in a dose-dependent manner, which showed a statistically significant difference compared with the PEDF treatment group. Conclusion. Our study is the first to demonstrate that NP-PEG-PEDF exert antiangiogenic effects on high glucose-stimulated HUVECs and have the potential to alleviate microvascular dysfunction. These data suggest that the NP-PEG-PEDF delivery system may offer an innovative therapeutic strategy for preventing neovascularization of the fundus. |
| format | Article |
| id | doaj-art-6c25a3bfbd0749a2ae676f70255df7f1 |
| institution | Kabale University |
| issn | 2314-6753 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-6c25a3bfbd0749a2ae676f70255df7f12025-02-03T01:22:45ZengWileyJournal of Diabetes Research2314-67532022-01-01202210.1155/2022/1193760Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for NeovascularizationFeng Zhao0Wenlei Fei1Zhouyue Li2Hanyang Yu3Lei Xi4Guangdong Provincial People’s HospitalGuangdong Provincial People’s HospitalState Key Laboratory of OphthalmologyState Key Laboratory of OphthalmologyGuangdong Provincial People’s HospitalBackground. Pathological neovascularization, which involves a disruption in the balance between angiogenic and antiangiogenic factors under pathological conditions, is the basis of many intraocular diseases. Pigment epithelium-derived factor (PEDF) is a potent natural, endogenous inhibitor of neovascularization because of its antiangiogenic and neuroprotective benefits. However, its application is restricted by its instability and short half-life. The present study is aimed at investigating the cytotoxicity and antiangiogenic effects of PEDF-loaded PEGylated nanoparticles (NP-PEG-PEDF) on high glucose-stimulated human umbilical vein endothelial cells (HUVECs). Methods. In this study, NP-PEG-PEDF were fabricated using the multiple emulsion method for the first time. HUVECs were cultured in a high concentration of glucose (30 mmol/L D-glucose), simulating diabetic conditions. The antiangiogenic effects of vascular endothelial growth factor (VEGF), pure PEDF, and NP-PEG-PEDF on proliferation, migration, and tube formation were evaluated. VEGF secretion in high glucose-stimulated HUVECs was further tested in vitro. Results. NP-PEG-PEDF exhibited low cytotoxicity in HUVECs. Our results indicated that in vitro, NP-PEG-PEDF attenuated diabetes-induced HUVEC proliferation, migration, and tube formation and suppressed VEGF secretion. The apoptosis of diabetes-induced HUVECs occurred in a dose-dependent manner, which showed a statistically significant difference compared with the PEDF treatment group. Conclusion. Our study is the first to demonstrate that NP-PEG-PEDF exert antiangiogenic effects on high glucose-stimulated HUVECs and have the potential to alleviate microvascular dysfunction. These data suggest that the NP-PEG-PEDF delivery system may offer an innovative therapeutic strategy for preventing neovascularization of the fundus.http://dx.doi.org/10.1155/2022/1193760 |
| spellingShingle | Feng Zhao Wenlei Fei Zhouyue Li Hanyang Yu Lei Xi Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization Journal of Diabetes Research |
| title | Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization |
| title_full | Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization |
| title_fullStr | Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization |
| title_full_unstemmed | Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization |
| title_short | Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization |
| title_sort | pigment epithelium derived factor loaded pegylated nanoparticles as a new antiangiogenic therapy for neovascularization |
| url | http://dx.doi.org/10.1155/2022/1193760 |
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