Targeted dexamethasone nano-prodrug for corneal neovascularization management.
Targeted dexamethasone nano-prodrug for corneal neovascularization management.
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靶向地塞米松纳米生产物用于角膜新血管化管理。
DOI：
10.1016/j.bj.2023.03.005
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发表时间：
2024-02
影响因子：
5.5
通讯作者：
Shentu, Xiangchao
中科院分区：
文献类型：
--
作者：
Yin, Qichuan;Han, Haijie;Shi, Kexin;Zhou, Jiayue;Zheng, Sifan;Yao, Ke;Shentu, Xiangchao
关键词：
为了克服传统疗法治疗角膜新生血管（CNV）的缺点，我们评估了聚乙二醇（PEG）缀合的丙氨酸-脯氨酸-精氨酸-脯氨酸-甘氨酸（APRPG）肽修饰的地塞米松（Dex）的疗效，这是一种新型纳米前药（Dex-PEG-APRPG，DPA）。通过透射电子显微镜 (TEM) 和动态光散射 (DLS) 分析测量 DPA 纳米前药的表征。在体外评估了 DPA 的细胞毒性以及对细胞迁移和管形成的影响。采用角膜碱烧伤法建立小鼠CNV模型。受伤的角膜每天滴三次 DPA (0.2 mM)、Dex 溶液 (0.2 mM)、Dexp (2 mM) 或生理盐水滴眼液。两周后，取出眼睛进行组织病理学、免疫染色和 mRNA 表达分析。 DPA平均直径为30 nm，细胞毒性小，眼部生物相容性良好。更重要的是，DPA 对血管内皮细胞表现出特异性靶向，可有效抑制细胞迁移和管形成。在小鼠CNV模型中，临床、组织学和免疫组化检查结果显示，DPA比Dex具有更强的血管生成抑制作用，类似于浓度高出一个数量级的临床药物。这归因于角膜中促血管生成和促炎症因子表达的显着下调。体内成像结果还表明 APRPG 可以延长眼睛停留时间。本研究表明DPA纳米前药较传统疗法具有特异性靶向能力和更高的生物利用度等优势，在安全、高效的CNV治疗方面具有巨大潜力。
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). 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. 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. 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.
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影响因子：
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作者：
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发表时间：
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期刊：
The ocular surface
影响因子：
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