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Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for
Feng Zhao1,2, Wenlei Fei1, Zhouyue Li2
1Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
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.
Insights
PEGylated nanoparticles loaded with pigment epithelium-derived factor (PEDF) show promise in combating pathological neovascularization by reducing endothelial cell dysfunction and inhibiting blood vessel growth.
Area of Science:
- Biomedical Engineering
- Ophthalmology
- Cell Biology
Background:
- Pathological neovascularization underlies many intraocular diseases, driven by an imbalance in angiogenic factors.
- Pigment epithelium-derived factor (PEDF) is a natural antiangiogenic and neuroprotective agent, but its clinical use is limited by instability.
- Developing stable delivery systems for PEDF is crucial for treating neovascularization.
Purpose of the Study:
- To investigate the antiangiogenic effects and cytotoxicity of PEDF-loaded PEGylated nanoparticles (NP-PEG-PEDF).
- To evaluate NP-PEG-PEDF in high glucose-stimulated human umbilical vein endothelial cells (HUVECs) as a model for diabetic conditions.
- To assess the potential of NP-PEG-PEDF as a therapeutic strategy for intraocular neovascular diseases.
Main Methods:
- Fabrication of NP-PEG-PEDF using the multiple emulsion method.
- Culture of HUVECs in high glucose (30 mmol/L D-glucose) to simulate diabetic conditions.
- Evaluation of antiangiogenic effects on HUVEC proliferation, migration, and tube formation, alongside VEGF secretion and apoptosis assays.
Main Results:
- NP-PEG-PEDF demonstrated low cytotoxicity in HUVECs.
- NP-PEG-PEDF significantly attenuated high glucose-induced HUVEC proliferation, migration, and tube formation.
- NP-PEG-PEDF suppressed VEGF secretion and induced dose-dependent apoptosis in diabetic HUVECs, outperforming pure PEDF.
Conclusions:
- NP-PEG-PEDF exhibit significant antiangiogenic properties against high glucose-stimulated HUVECs.
- This novel delivery system shows potential for alleviating microvascular dysfunction and preventing fundus neovascularization.
- NP-PEG-PEDF represent an innovative therapeutic approach for intraocular diseases characterized by pathological neovascularization.
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