体内
结直肠癌
药代动力学
肽
癌症研究
化学
癌症
内科学
医学
生物
生物化学
生物技术
作者
Hang Yu,Bo Wen,Huang Min,Feng Ren,Li-Bin Pan,Manyi Xu,Hao Lin,Lin Cong,Sen Zhang,Yan Li,Chi-Hin Cho,Chong‐Jing Zhang,Xiaoguang Chen,Yan Wang
标识
DOI:10.1016/j.cclet.2023.108235
摘要
A nine cyclic peptide (TCP-1) showed excellent specificity for colon cancer. TCP-1 binds with human tumor tissues at early stages and mice tumor with diameters of 1-4 mm, suggesting that TCP-1 may be used for early diagnosis of colon cancer. The mechanism of the targeted binding of TCP-1 to colon cancer was also studied using immunoprecipitation, LC-MS and bioinformatics. After screening and identifying of the possible binding target proteins of TCP-1, keratin, type II cytoskeletal 5 was speculated to be the specific binding target protein of TCP-1 in human tumor tissue. Pharmacokinetics studies were conducted to investigate the target-mediated drug disposition of the new tumor-specific peptide by LC-MS/MS. The tissue distribution study showed that TCP-1 was found only in colon tumors (the target site) in tumor mice did not bind to any other tissues. Conjugating TCP-1 to tumor markedly increased its removal rate from blood circulation but mildly extended its staying time in vivo. In tumor mice, a lower AUC of TCP-1 (reduced by almost 35%) and 2-fold higher clearance were found compared to that of normal mice. The proposed metabolic pathway of TCP-1 in the kidney was also determined using LC-MSn-IT-TOF. The high specificity and low toxicity of the peptide may be caused by its extremely tight binding to the targets. Potential applications for future clinical use, including MRI and PET/CT were also explored, and this research may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.
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