De Novo Computational Design for Development of a Peptide Ligand Oriented to VEGFR-3 with High Affinity and Long Circulation
| Autor: | Li X. Liu, Tao Lu, Ming S. Lin, Yue Wang, Xiao N. Ma, Bing X. Li, Zhi P Dong, Hong M. Li, Qi Y. Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Biodistribution Cell Fluorescent Antibody Technique Pharmaceutical Science Peptide Kidney Ligands Mice 03 medical and health sciences In vivo Cell Line Tumor Drug Discovery medicine Animals Humans Peptide library Radioisotopes chemistry.chemical_classification A549 cell Vascular Endothelial Growth Factor Receptor-3 Rats 030104 developmental biology medicine.anatomical_structure chemistry Biochemistry A549 Cells Drug delivery Molecular Medicine Female Peptides Immunostaining HeLa Cells |
| Zdroj: | Molecular Pharmaceutics. 14:2236-2244 |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | The overexpression of VEGFR-3 is correlated with a worse prognosis in lung cancer and has been regarded as a rational target for specific drug delivery. Here, VEGFR-3 homing peptide library was efficiently established by computational design. Strong fluorescent signals of selected peptides were observed in A549 cells, but much weaker in other cells. The positive immunostaining overlapped with VEGFR-3 confirmed high affinity and selectivity of one novel peptide (CP-7). In addition, cell uptake of FITC–CP-7 peptide was significantly blocked by coinjection of excess CP-7 peptide. After labeled with 131I, the profile of pharmacology and biodistribution could be traced in vivo. The 131I-radiolabeled CP-7 peptide conjugates were >85% stable in serum over 4 h and exhibited a specific uptake of 18.04 ± 2.04% ID/g at 0.5 h after injection to high VEGFR-3 expressing A549 tumor mice. More importantly, lower uptake concentration in heart (1.06 ± 0.15% ID/g) after 2 h demonstrated the safety of peptide in vivo. The hi... |
| Databáze: | OpenAIRE |
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