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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\u2009mmol\/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.<\/jats:p>","DOI":"10.1155\/2022\/1193760","type":"journal-article","created":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T14:35:08Z","timestamp":1650638108000},"page":"1-9","source":"Crossref","is-referenced-by-count":5,"title":["Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-3014","authenticated-orcid":true,"given":"Feng","family":"Zhao","sequence":"first","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"},{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1354-0845","authenticated-orcid":true,"given":"Wenlei","family":"Fei","sequence":"additional","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1069-0581","authenticated-orcid":true,"given":"Zhouyue","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8725-1333","authenticated-orcid":true,"given":"Hanyang","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8403-910X","authenticated-orcid":true,"given":"Lei","family":"Xi","sequence":"additional","affiliation":[{"name":"Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"volume-title":"Wet age-related macular degeneration (Wet AMD)","year":"2021","author":"S. 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