VPAC receptor mediated tumor cell targeting by protamine based nanoparticles
| Autor: | Gottfried Köhler, Franz Hajos, Michael Edetsberger, Andreas Zimmer, Raphaela E. Kaisler, Anna Ortner, Karin Wernig, Wilhelm Mosgoeller |
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| Rok vydání: | 2010 |
| Předmět: |
Receptors
Vasoactive Intestinal Polypeptide Type I media_common.quotation_subject Vasoactive intestinal peptide Cell Pharmaceutical Science Biology In Vitro Techniques Drug Stability In vivo Cell Line Tumor Neoplasms medicine Animals Humans Protamines Particle Size Internalization Receptor media_common Arteries Protamine Immunohistochemistry Cell biology Rats Vasodilation medicine.anatomical_structure Spectrometry Fluorescence Biochemistry Cell culture biology.protein Nanoparticles Receptors Vasoactive Intestinal Peptide Type II hormones hormone substitutes and hormone antagonists Ex vivo Receptors Pituitary Adenylate Cyclase-Activating Polypeptide Type I Vasoactive Intestinal Peptide |
| Zdroj: | Journal of drug targeting. 18(6) |
| ISSN: | 1029-2330 |
| Popis: | The receptors for vasoactive intestinal peptide (VIP), VPAC1-, VPAC2-, and PAC1-receptor are overexpressed by various tumor cells. VIP can target these receptors and transport conjugates into the cell. However, the use of VIP for tumor cell targeting is hampered by the peptides short half-lives due to enzymatic degradation. Because protamine-based nanoparticles (proticles) protect the peptide and serve as peptide depot, we explored the potential of proticles as carrier for VIP-conjugated molecules. The VIP-loaded proticles were stable as shown by Fluorescence Correlation Spectroscopy. With Confocal Laser Scanning Microscopy, we observed VIP-loaded proticles to specifically target the tumor cells. The cell binding triggered the substance release and conjugate internalization of VIP-Cy3 in vitro and ex vivo by human tumors. We observed VIP releasing proticle depots distributed in rat tissue and human tumors. Our findings warrant further studies to explore the proticles potential to enable peptide-mediated targeting for in vivo and clinical applications. |
| Databáze: | OpenAIRE |
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