结直肠癌
生物素化
癌症
癌症研究
医学
淘选
体内
靶向给药
药物输送
肽库
肽
靶向治疗
药理学
药品
化学
生物
内科学
生物化学
肽序列
有机化学
生物技术
基因
作者
Chien‐Hsun Wu,Yi-Huei Kuo,Ruey‐Long Hong,Han‐Chung Wu
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2015-06-03
卷期号:7 (290)
被引量:51
标识
DOI:10.1126/scitranslmed.aaa9391
摘要
Colorectal cancer is one of the most commonly diagnosed cancers and a leading cause of cancer mortality worldwide. Current treatment for colorectal cancer results in only limited success, and more effective therapeutic approaches are thus urgently needed. The development of new methods for early detection and effective treatments for cancer is contingent on the identification of biomarkers on the surface of cancer cells, as well as isolation of tumor-specific ligands with high binding affinity to such biomarkers. In vitro biopanning of a phage-displayed peptide library was used to identify specific peptides binding to human colorectal carcinoma cells. The targeting peptide pHCT74 showed the greatest potential for drug delivery in both in vitro and in vivo studies. The use of biotinylated peptides combined with an affinity trapping method and liquid chromatography-tandem mass spectrometry identified the target protein for the pHCT74 peptide as α-enolase. In animal model studies, combined pHCT74-conjugated liposomal doxorubicin (pHCT74-LD) and pHCT74-conjugated liposomal vinorelbine (pHCT74-sLV) therapy exhibited an enhanced antitumor effect and markedly extended the survival of mice with human colorectal cancer in subcutaneous and orthotopic models. Our findings indicate that α-enolase-targeted lipid nanoparticles have great potential for application in targeted drug delivery systems for colorectal cancer therapy.
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