α-Enolase-binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer
Journal
Science Translational Medicine
Journal Volume
7
Journal Issue
290
Date Issued
2015
Author(s)
Abstract
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.
SDGs
Other Subjects
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
Publisher
American Association for the Advancement of Science
Type
journal article