Targeted dexamethasone nano-prodrug for corneal neovascularization management
Background: To overcome the drawbacks of traditional therapy for corneal neovascularization (CNV), we evaluated the efficacy of polyethylene glycol (PEG)-conjugated Ala-Pro-Arg-Pro-Gly (APRPG) peptide modified dexamethasone (Dex), a novel nano-prodrug (Dex-PEG-APRPG, DPA). Methods: Characterization...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Biomedical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S231941702300029X |
| _version_ | 1797242959347843072 |
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| author | Qichuan Yin Haijie Han Kexin Shi Jiayue Zhou Sifan Zheng Ke Yao Xingchao Shentu |
| author_facet | Qichuan Yin Haijie Han Kexin Shi Jiayue Zhou Sifan Zheng Ke Yao Xingchao Shentu |
| author_sort | Qichuan Yin |
| collection | DOAJ |
| description | Background: To overcome the drawbacks of traditional therapy for corneal neovascularization (CNV), we evaluated the efficacy of polyethylene glycol (PEG)-conjugated Ala-Pro-Arg-Pro-Gly (APRPG) peptide modified dexamethasone (Dex), a novel nano-prodrug (Dex-PEG-APRPG, DPA). Methods: Characterization of DPA nano-prodrug were measured with transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses. Cytotoxicity and effects on cell migration and tube formation of DPA were evaluated in vitro. A murine CNV model was established by cornea alkali burn. The injured corneas were given eye drops of DPA (0.2 mM), Dex solution (0.2 mM), Dexp (2 mM), or normal saline three times a day. After two weeks, eyes were obtained for the analysis of histopathology, immunostaining, and mRNA expression. Results: DPA with an average diameter of 30 nm, presented little cytotoxicity and had good ocular biocompatibility. More importantly, DPA showed specific targeting to vascular endothelial cells with efficient inhibition on cell migration and tube formation. In a mouse CNV model, clinical, histological, and immunohistochemical examination results revealed DPA had a much stronger angiogenesis suppression than Dex, resembling a clinical drug with an order of magnitude higher concentration. This was ascribed to the significant downregulations in the expression of pro-angiogenic and pro-inflammatory factors in the corneas. In vivo imaging results also demonstrated that APRPG could prolong ocular retention time. Conclusions: This study suggests that DPA nano-prodrug occupies advantages of specific targeting ability and improved bioavailability over conventional therapy, and holds great potential for safe and efficient CNV therapy. |
| first_indexed | 2024-03-08T14:21:12Z |
| format | Article |
| id | doaj.art-82ba17bc8a624998883b9fecc3921049 |
| institution | Directory Open Access Journal |
| issn | 2319-4170 |
| language | English |
| last_indexed | 2024-04-24T18:47:30Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedical Journal |
| spelling | doaj.art-82ba17bc8a624998883b9fecc39210492024-03-27T04:52:17ZengElsevierBiomedical Journal2319-41702024-02-01471100592Targeted dexamethasone nano-prodrug for corneal neovascularization managementQichuan Yin0Haijie Han1Kexin Shi2Jiayue Zhou3Sifan Zheng4Ke Yao5Xingchao Shentu6Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, ChinaEye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, ChinaEye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, ChinaEye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, ChinaGKT School of Medical Education, King’s College London, London, SE1 1UL, England, UKEye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, China; Corresponding author. Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd., Hangzhou 310009, China.Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Lab of Ophthalmology, Zhejiang University, Hangzhou, China; Corresponding author. Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd., Hangzhou 310009, China.Background: To overcome the drawbacks of traditional therapy for corneal neovascularization (CNV), we evaluated the efficacy of polyethylene glycol (PEG)-conjugated Ala-Pro-Arg-Pro-Gly (APRPG) peptide modified dexamethasone (Dex), a novel nano-prodrug (Dex-PEG-APRPG, DPA). Methods: Characterization of DPA nano-prodrug were measured with transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses. Cytotoxicity and effects on cell migration and tube formation of DPA were evaluated in vitro. A murine CNV model was established by cornea alkali burn. The injured corneas were given eye drops of DPA (0.2 mM), Dex solution (0.2 mM), Dexp (2 mM), or normal saline three times a day. After two weeks, eyes were obtained for the analysis of histopathology, immunostaining, and mRNA expression. Results: DPA with an average diameter of 30 nm, presented little cytotoxicity and had good ocular biocompatibility. More importantly, DPA showed specific targeting to vascular endothelial cells with efficient inhibition on cell migration and tube formation. In a mouse CNV model, clinical, histological, and immunohistochemical examination results revealed DPA had a much stronger angiogenesis suppression than Dex, resembling a clinical drug with an order of magnitude higher concentration. This was ascribed to the significant downregulations in the expression of pro-angiogenic and pro-inflammatory factors in the corneas. In vivo imaging results also demonstrated that APRPG could prolong ocular retention time. Conclusions: This study suggests that DPA nano-prodrug occupies advantages of specific targeting ability and improved bioavailability over conventional therapy, and holds great potential for safe and efficient CNV therapy.http://www.sciencedirect.com/science/article/pii/S231941702300029XCorneal neovascularizationDexamethasoneNano-prodrugAngiogenic vessel-homing peptideTargeted drug delivery |
| spellingShingle | Qichuan Yin Haijie Han Kexin Shi Jiayue Zhou Sifan Zheng Ke Yao Xingchao Shentu Targeted dexamethasone nano-prodrug for corneal neovascularization management Biomedical Journal Corneal neovascularization Dexamethasone Nano-prodrug Angiogenic vessel-homing peptide Targeted drug delivery |
| title | Targeted dexamethasone nano-prodrug for corneal neovascularization management |
| title_full | Targeted dexamethasone nano-prodrug for corneal neovascularization management |
| title_fullStr | Targeted dexamethasone nano-prodrug for corneal neovascularization management |
| title_full_unstemmed | Targeted dexamethasone nano-prodrug for corneal neovascularization management |
| title_short | Targeted dexamethasone nano-prodrug for corneal neovascularization management |
| title_sort | targeted dexamethasone nano prodrug for corneal neovascularization management |
| topic | Corneal neovascularization Dexamethasone Nano-prodrug Angiogenic vessel-homing peptide Targeted drug delivery |
| url | http://www.sciencedirect.com/science/article/pii/S231941702300029X |
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