Novel peptides functionally targeting in vivo human lung cancer discovered by in vivo peptide displayed phage screening.
Amino Acids
; 47(2): 281-9, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25366491
ABSTRACT
Discovery of the cancer-specific peptidic ligands have been emphasized for active targeting drug delivery system and non-invasive imaging. For the discovery of useful and applicable peptidic ligands, in vivo peptide-displayed phage screening has been performed in this study using a xenograft mouse model as a mimic microenvironment to tumor. To seek human lung cancer-specific peptides, M13 phage library displaying 2.9 × 10(9) random peptides was intravenously injected into mouse model bearing A549-derived xenograft tumor through the tail vein. Then the phages emerged from a course of four rounds of biopanning in the xenograft tumor tissue. Novel peptides were categorized into four groups according to a sequence-homology phylogenicity, and in vivo tumor-targeting capacity of these peptides was validated by whole body imaging with Cy5.5-labeled phages in various cancer types. The result revealed that novel peptides accumulated only in adenocarcinoma lung cancer cell-derived xenograft tissue. For further confirmation of the specific targeting ability, in vitro cell-binding assay and immunohistochemistry in vivo tumor tissue were performed with a selected peptide. The peptide was found to bind intensely to lung cancer cells both in vitro and in vivo, which was efficiently compromised with unlabeled phages in an in vitro competition assay. In conclusion, the peptides specifically targeting human lung cancer were discovered in this study, which is warranted to provide substantive feasibilities for drug delivery and imaging in terms of a novel targeted therapeutics and diagnostics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistemas de Liberação de Medicamentos
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Biblioteca de Peptídeos
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Microambiente Tumoral
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Neoplasias Pulmonares
/
Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Amino Acids
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2015
Tipo de documento:
Article