Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment
Selective targeting and photocoagulation of ocular angiogenesis mediated by a phage-derived human antibody fragment
复制标题
DOI：
10.1038/13679
复制
发表时间：
1999-10-01
影响因子：
46.9
通讯作者：
Neri, D
中科院分区：
文献类型：
--
作者：
Birchler, M;Viti, F;Neri, D
选择性靶向和闭塞新血管的分子将有助于诊断和治疗与血管生成相关的病理。我们发现，噬菌体衍生的人抗体片段 (L19) 对纤连蛋白的 ED-B 结构域（血管生成的标志物）具有高亲和力，可选择性地定位于兔眼血管生成模型中新形成的血管。 L19 抗体与光敏剂化学偶联并用红光照射，介导眼部新生血管的完全选择性闭塞，并促进相应内皮细胞的凋亡。这些结果表明，新的眼部血管可以通过免疫化学方法与先前存在的血管区分开来，并表明光敏剂的靶向递送可能有效治疗血管生成相关的病理。
Molecules that selectively target and occlude new blood vessels would be useful for diagnosis and treatment of pathologies associated with angiogenesis. We show that a phage-derived human antibody fragment (L19) with high affinity for the ED-B domain of fibronectin, a marker of angiogenesis, selectively localizes to newly formed blood vessels in a rabbit model of ocular angiogenesis. The L19 antibody, chemically coupled to a photosensitizer and irradiated with red light, mediates complete and selective occlusion of ocular neovasculature and promotes apoptosis of the corresponding endothelial cells. These results demonstrate that new ocular blood vessels can be distinguished immunochemically from preexisting ones and suggest that the targeted delivery of photosensitizers may be effective in treating angiogenesis-related pathologies.