A peptide-based carrier for intracellular delivery of proteins into malignant glial cells in vitro
| Autor: | Jerome Boulaire, Hui Min Beh, Seong Loong Lo, Chunxiao Wu, Shu Wang, Doreen Siu Yi Leung, Michelle Hong |
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| Rok vydání: | 2007 |
| Předmět: |
Phage display
Molecular Sequence Data Pharmaceutical Science Peptide Receptors Cell Surface Biopanning Biology Transfection Bacteriophage Peptide Library Cell Line Tumor Humans Amino Acid Sequence Peptide library Peptide sequence chemistry.chemical_classification Drug Carriers Proteins Carbocyanines biology.organism_classification beta-Galactosidase Endocytosis Biochemistry chemistry Cell culture Astrocytes Glioblastoma Neuroglia Protein Binding |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 130(2) |
| ISSN: | 1873-4995 |
| Popis: | Aiming at identification of novel peptides that can be employed for effective targeting of malignant gliomas, we used a 12-mer peptide phage display library and cultured human malignant glioma cells for phage selection. Several common phage clones emerged after 4 rounds of biopanning against the U87MG glioblastoma cell line. The most abundant phage clone VTW, expressing a sequence of VTWTPQAWFQWV, bound to U87MG cells 700-fold more efficiently than the original unselected library. The VTW phage also bound strongly to other human glioma cell lines, including H4, SW1088 and SW1783, but very weakly to normal human astrocytes and SV40-immortalized human astroglial cells. When compared to other non-glial tumor cells, the phage showed 400- to 1400-fold higher binding efficiency for U87MG cells. After linked to positively charged lysine peptides, the VTW peptide became water soluble and was able to deliver biologically active, hydrophilic beta-galactosidase into U87MG cells, with up to 90% of the cells being stained intensively blue. This peptide carrier did not show obvious protein delivery activities in the human astrocytes. Our results provide a proof of principle to the concept that peptides identified through phage display technology can be used to develop protein carriers that are capable of mediating intracellular delivery of hydrophilic macromolecules in a tumor cell-specific manner. |
| Databáze: | OpenAIRE |
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