Identification of novel carrier peptides for the specific delivery of therapeutics into cancer cells
- 17 December 2002
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 17 (2) , 256-258
- https://doi.org/10.1096/fj.02-0280fje
Abstract
Cancer therapy is currently limited by the difficulty of achieving efficient delivery into target cells. To investigate whether therapeutics can be delivered specifically to cancer cells, we have explored the possibility of selecting small peptides that bind specifically, or preferentially, to breast cancer cell lines. By using random peptide phage libraries and an experimental approach that allows the selection of internalized peptides, cell-specific binding peptides have been identified. The peptides define a major core motif (LTVXPWY) that was not found in negative phages. Phage displaying LTVSPWY peptide sequence exhibited a specific binding to breast cancer cells. None of the selected peptides bound to human primary cells from different tissue origin (e.g., epithelial, endothelial, hematopoetic). The potential of the selected peptides to mediate cellular internalization in the context of phages and recombinant GFP-peptide fusions was demonstrated. By linking the LTVSPWY peptide to an antisense phosphorothioate oligonucleotide against the ErbB2 receptor, specific delivery to cancer cells was achieved. In contrast to free antisense, the peptide-antisense conjugates inhibited ErbB2 gene expression. Thus, efficient delivery of antisense oligonucleotides can be achieved by coupling them to cancer cell-specific peptides, identified by a method that did not require any knowledge about their corresponding receptors.Keywords
This publication has 37 references indexed in Scilit:
- Translocating peptides and proteins and their use for gene deliveryCurrent Opinion in Biotechnology, 2000
- Adeno-Associated Viruses as Gene Transfer VehiclesPublished by S. Karger AG ,2000
- Generating improved single-chain Fv molecules for tumor targetingJournal of Immunological Methods, 1999
- Non-Viral Peptide-Based Approaches to Gene DeliveryJournal of Drug Targeting, 1999
- Nucleic Acid Therapeutics: State of the Art and Future ProspectsBlood, 1998
- Viral vectors for gene therapyTrends in Biotechnology, 1998
- Sterically Stabilized Anti-HER2 Immunoliposomes: Design and Targeting to Human Breast Cancer Cells in VitroBiochemistry, 1997
- Gene therapy of metastatic cancer by in vivo retroviral gene targetingNature Genetics, 1995
- Tissue-Specific Targeting of Retroviral Vectors Through Ligand-Receptor InteractionsScience, 1994
- Cure of Xenografted Human Carcinomas by BR96-Doxorubicin ImmunoconjugatesScience, 1993