https://scholars.lib.ntu.edu.tw/handle/123456789/551235
標題: | α-Enolase-binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer | 作者: | Wu C.-H. Kuo Y.-H. RUEY-LONG HONG Wu H.-C. |
公開日期: | 2015 | 出版社: | American Association for the Advancement of Science | 卷: | 7 | 期: | 290 | 來源出版物: | Science Translational Medicine | 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. ? 2015, American Association for the Advancement of Science. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930434155&doi=10.1126%2fscitranslmed.aaa9391&partnerID=40&md5=18e27b6c58ca882614392349a51ca0a8 https://scholars.lib.ntu.edu.tw/handle/123456789/551235 |
ISSN: | 1946-6234 | DOI: | 10.1126/scitranslmed.aaa9391 | SDG/關鍵字: | alpha enolase; doxorubicin; nanocarrier; navelbine; peptide derivative; peptide pHCT74; unclassified drug; enolase; peptide; animal experiment; animal model; animal tissue; antineoplastic activity; area under the curve; Article; biopanning; biotinylation; cancer inhibition; cancer survival; carcinoma cell; colorectal cancer; colorectal carcinoma; controlled study; drug blood level; drug cytotoxicity; drug delivery system; drug distribution; drug efficacy; drug tumor level; HCT116 cell line; human; human cell; IC50; in vitro study; in vivo study; liquid chromatography; mouse; nonhuman; peptide library; phage display; priority journal; protein binding; protein targeting; tandem mass spectrometry; amino acid sequence; chemistry; Colorectal Neoplasms; drug screening; metabolism; molecular genetics; sequence homology; tissue distribution; validation study; Amino Acid Sequence; Colorectal Neoplasms; Drug Delivery Systems; Humans; Molecular Sequence Data; Peptides; Phosphopyruvate Hydratase; Sequence Homology, Amino Acid; Tissue Distribution; Xenograft Model Antitumor Assays |
顯示於: | 腫瘤醫學研究所 |
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