Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics
Identification and characterization of a novel peptide ligand of epidermal growth factor receptor for targeted delivery of therapeutics
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DOI：
10.1096/fj.05-4058com
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发表时间：
2005-12-01
期刊：
影响因子：
4.8
通讯作者：
Gu, JR
中科院分区：
文献类型：
--
作者：
Li, ZH;Zhao, RJ;Gu, JR
表皮生长因子受体（ErbB1、EGFR）在多种人类癌细胞中过度表达。它被认为是药物递送的合理靶标。为了鉴定具有 EGFR 特异性结合能力的新型配体，我们筛选了噬菌体展示肽库，发现了编码氨基酸序列 YHWYGYT-PQNVI 的富集噬菌体克隆（指定为 GE11）。竞争性结合测定和斯卡查德分析表明，GE11 肽与 EGFR 特异性且有效地结合，解离常数类似于 22 nM，但促有丝分裂活性比 EGF 低得多。我们发现，这些肽优先内化到 EGFR 高表达细胞中，并且在静脉注射后，它们在 EGFR 过表达肿瘤异种移植物中积累。体内递送。在基因递送研究中，GE11 缀合的聚乙烯亚胺 (PEI) 载体的有丝分裂活性较低，但在将基因转染到 EGFR 高表达细胞和肿瘤异种移植物中仍然相当有效。总而言之，GE11 是一种潜在安全且有效的靶向部分，用于通过 EGFR 介导的选择性药物递送系统。
Epidermal growth factor receptor (ErbB1, EGFR) is overexpressed in a variety of human cancer cells. It has been considered as a rational target for drug delivery. To identify novel ligands with specific binding capabilities to EGFR, we screened a phage display peptide library and found an enriched phage clone encoding the amino acid sequence YHWYGYT-PQNVI (designated as GE11). Competitive binding assay and Scatchard analysis revealed that GE11 peptide bound specifically and efficiently to EGFR with a dissociation constant of similar to 22 nM, but with much lower mitogenic activity than with EGF. We showed that the peptides were internalized preferentially into EGFR highly expressing cells, and they accumulated in EGFR overexpressing tumor xenografts after i.v. delivery in vivo. In gene delivery studies, GE11-conjugated polyethylenimine (PEI) vectors were less mitogenic, but still quite efficient at transfecting genes into EGFR highly expressing cells and tumor xenografts. Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR.