Tumor specifically internalizing peptide ‘HN-1’: Targeting the putative receptor retinoblastoma-regulated discoidin domain receptor 1 involved in metastasis  

作　　者：Frank-Un Hong Miguel Castro Klaus Linse 

机构地区：[1]Research&Development,Bio-Synthesis,Inc.,Lewisville,TX 75057,United States

出　　处：《World Journal of Clinical Oncology》2022年第5期323-338,共16页世界临床肿瘤学杂志（英文版）

摘　　要：BACKGROUND Less than 0.5%of intravenously injected drugs reach tumors,contributing to side effects.To limit damage to healthy cells,various delivery vectors have been formulated;yet,previously developed vectors suffer from poor penetration into solid tumors.This issue was resolved by the discovery of HN-1 peptide isolated via biopanning a phage-display library.HN-1 targets human head and neck squamous cell carcinoma(HNSCC)(breast,thyroid;potentially lung,cervix,uterine,colon cancer),translocates across the cell membrane,and efficiently infiltrates solid tumors.HN-1 peptide has been conjugated to various anticancer drugs and imaging agents though the identity of its receptor remained enigmatic.AIM To decipher the clues that pointed to retinoblastoma(Rb)-regulated discoidindomain receptor 1 as the putative receptor for HN-1 is described.METHODS HN-1 peptide was synthesized and purified using reverse-phase highperformance liquid chromatography and gel electrophoresis.The predicted mass was confirmed by mass spectroscopy.To image the 3-dimensional structure of HN-1 peptide,PyMOL was used.Molecular modeling was also performed with PEP-FOLD3 software via RPBS bioinformatics web portal(INSERM,France).The immunohistochemistry results of discoidin domain receptor 1(DDR1)protein were obtained from the publicly accessible database in the Human Protein Atlas portal,which contained the images of immunohistochemically labeled human cancers and the corresponding normal tissues.RESULTS The clues that led to DDR1 involved in metastasis as the putative receptor mediating HN-1 endocytosis are the following:(1)HN-1 is internalized in phosphate-buffered saline and its uptake is competitively inhibited;(2)HN-1(TSPLNIHNGQKL)exhibits similarity with a stretch of amino acids in alpha5 beta3 integrin(KLLITIHDRKEF).Aside from two identical residues(Ile-His)in the middle,the overall distribution of polar and nonpolar residues throughout the sequences is nearly identical.As HN-1 sequence lacks the Arg-Gly-Asp motif recognized by integrins,HN

关 键 词：HN-1 peptide Solid tumor Targeted drug delivery Discoidin domain receptor 1 Tyrosine kinase METASTASIS 

分 类 号：R73-36[医药卫生—肿瘤]