title: α-Enolase-binding peptide enhances drug delivery efficiency and therapeutic efficacy against colorectal cancer.
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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Chien-Hsun
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yi-Huei
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Ruey-Long
authors.initials: RL
authors.lastname: Hong
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan. hcw0928@gate.sinica.edu.tw.
authors.forename: Han-Chung
authors.initials: HC
authors.lastname: Wu
mesh_terms: D000595:Amino Acid Sequence; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D010455:Peptides; D010751:Phosphopyruvate Hydratase