Anti-angiogenesis through noninvasive to minimally invasive intraocular delivery of the peptide CC12 identified by in vivo-directed evolution
Anti-angiogenesis through noninvasive to minimally invasive intraocular delivery of the peptide CC12 identified by in vivo-directed evolution
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DOI：
10.1016/j.biomaterials.2016.09.022
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发表时间：
2017-01-01
期刊：
影响因子：
14
通讯作者：
Xu, X.
中科院分区：
文献类型：
--
作者：
Chen, Chong;Liu, Kun;Xu, X.
抗血管内皮生长因子（VEGF）疗法广泛用于治疗新生血管性眼底疾病，例如糖尿病性视网膜病变。然而，这些药物需要玻璃体内注射，因为它们的强亲水性和高分子量阻止它们穿透细胞膜和复杂的组织屏障。此外，所需的重复注射可能导致感染和组织损伤。在这项研究中，我们使用体内定向进化噬菌体展示技术，以确定一种新的十二肽，命名为CC12，具有穿透眼屏障的能力，在一个非侵入性（通过结膜囊滴注）或微创（通过球后注射）的方式。KV11，一种先前被证明能抑制视网膜中病理性新生血管形成的抗血管生成肽，然后被用作CC12的模型抗血管生成货物。我们发现，KV 11肽与CC12肽的缀合促进了KV 11向视网膜的递送，导致通过局部应用显著抑制视网膜新生血管形成而没有组织毒性。总的来说，我们的多层次评价数据表明，CC12可以使非侵入性的抗血管生成治疗剂的微创眼内输送。(C)2016爱思唯尔有限公司版权所有。
Anti-vascular endothelial growth factor (VEGF) therapies are widely used for the treatment of neovascular fundus diseases such as diabetic retinopathy. However, these agents need to be injected intravitreally, because their strong hydrophilicity and high molecular weight prevent them from penetrating cell membranes and complex tissue barriers. Moreover, the repeated injections that are required can cause infection and tissue injury. In this study, we used in vivo-directed evolution phage display technology to identify a novel dodecapeptide, named CC12, with the ability to penetrate the ocular barrier in a noninvasive (via conjunctival sac instillation) or minimally invasive (via retrobulbar injection) manner. KV11, an antiangiogenesis peptide previously demonstrated to inhibit pathological neovascularization in the retina, was then used as a model antiangiogenesis cargo for CC12. We found that conjugation of KV11 peptide with CC12 peptide facilitated the delivery of KV11 to the retina, resulting in significant inhibition of retinal neovascularization development via topical application without tissue toxicity. Collectively, our data of multilevel evaluations demonstrate that CC12 may enable the noninvasive to minimally invasive intraocular delivery of antiangiogenic therapeutics. (C) 2016 Elsevier Ltd. All rights reserved.