Active Targeting of Tumors through Conformational Epitope Imprinting
Active Targeting of Tumors through Conformational Epitope Imprinting
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通过构象表位印迹主动靶向肿瘤
DOI：
10.1002/anie.201412114
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发表时间：
2015-04-20
影响因子：
16.6
通讯作者：
Lu, Weiyue
中科院分区：
文献类型：
--
作者：
Zhang, Yan;Deng, Chunyue;Lu, Weiyue
大多数抗体识别构象表位是因为表位的特定三维形状而不是其线性结构，受到这一知识的启发，我们结合基于支架的肽设计和表面分子印迹来制造一种新型纳米载体，其具有捕获膜蛋白的稳定结合位点。在这项研究中，使用二硫键连接的含α螺旋的肽apamin来模拟蛋白质p32的胞外结构化N端部分，然后作为印记模板来生成亚40纳米大小的聚合物纳米颗粒，该颗粒能有效地与靶蛋白结合，识别p32阳性肿瘤细胞，并成功介导体内靶向光动力治疗。这可以为目前使用的肽修饰纳米载体提供一种有前途的替代品，并可能对针对多种人类疾病的基于聚合物纳米颗粒的疗法的开发产生广泛的影响。
Inspired by the knowledge that most antibodies recognize a conformational epitope because of the epitope's specific three-dimensional shape rather than its linear structure, we combined scaffold-based peptide design and surface molecular imprinting to fabricate a novel nanocarrier harboring stable binding sites that captures a membrane protein. In this study, a disulfide-linked a-helix-containing peptide, apamin, was used to mimic the extracellular, structured N-terminal part of the protein p32 and then serve as an imprinting template for generating a sub-40 nm-sized polymeric nano-particle that potently binds to the target protein, recognizes p32-positive tumor cells, and successfully mediates targeted photodynamic therapy in vivo. This could provide a promising alternative for currently used peptide-modified nanocarriers and may have a broad impact on the development of polymeric nanoparticle-based therapies for a wide range of human diseases.