Molecular engineering of high affinity single-chain antibody fragment for endothelial targeting of proteins and nanocarriers in rodents and humans
| Autor: | Mortimer Poncz, Jake S. Brenner, Vladimir R. Muzykantov, Ian Johnston, Makan Khoshnejad, Colin F. Greineder, Claudia Gottstein, Anning Yao, Elizabeth D. Hood |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Endothelium Antibody Affinity Pharmaceutical Science 02 engineering and technology Biology Article Cell Line 03 medical and health sciences Drug Delivery Systems In vivo Human Umbilical Vein Endothelial Cells medicine Animals Humans Single-chain variable fragment Amino Acid Sequence Endothelial Cells 021001 nanoscience & nanotechnology Molecular biology Transmembrane protein Rats Cell biology Platelet Endothelial Cell Adhesion Molecule-1 Endothelial stem cell 030104 developmental biology medicine.anatomical_structure Targeted drug delivery Liposomes Nanocarriers 0210 nano-technology Single-Chain Antibodies |
| Zdroj: | Journal of Controlled Release. 226:229-237 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2016.02.006 |
| Popis: | Endothelial cells (EC) represent an important target for pharmacologic intervention, given their central role in a wide variety of human pathophysiologic processes. Studies in lab animal species have established that conjugation of drugs and carriers with antibodies directed to surface targets like the Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, a highly expressed endothelial transmembrane protein) help to achieve specific therapeutic interventions in ECs. To translate such "vascular immunotargeting" to clinical practice, it is necessary to replace antibodies by advanced ligands that are more amenable to use in humans. We report the molecular design of a single chain variable antibody fragment (scFv) that binds with high affinity to human PECAM-1 and cross-reacts with its counterpart in rats and other animal species, allowing parallel testing in vivo and in human endothelial cells in microfluidic model. Site-specific modification of the scFv allows conjugation of protein cargo and liposomes, enabling their endothelial targeting in these models. This study provides a template for molecular engineering of ligands, enabling studies of drug targeting in animal species and subsequent use in humans. |
| Databáze: | OpenAIRE |
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