| Autor: |
Vigo M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain.; Biomedicine Doctorate Program, University of Barcelona, 08007, Spain., Haro-Martínez E; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain., Ruiz E; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain., Fumadó-Navarro J; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain., Placci M; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain.; Biotechnology Doctorate Program, University of Barcelona, 080007, Spain., Muro S; Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute for Science and Technology (BIST), Barcelona, 08028, Spain.; Institution of Catalonia for Research and Advanced Studies (ICREA), Barcelona, 08010, Spain.; Institute for Bioscience and Biotechnology Research and Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, USA. |
| Abstrakt: |
Intercellular adhesion molecule 1 (ICAM-1) is a cell-surface protein actively explored for targeted drug delivery. Anti-ICAM-1 nanocarriers (NCs) target ICAM-1-positive sites after intravenous injection in animal models, but quantitative mechanistic examination of cellular-level transport in vivo is not possible. Prior studies in human cell cultures indicated efficient uptake of these formulations via cell adhesion molecule-(CAM)-mediated endocytosis. However, ICAM-1 sequence differs among species; thus, whether anti-ICAM-1 NCs induce similar behavior in animal cells, key for intracellular drug delivery, is unknown. To begin bridging this gap, we first qualitatively verified intracellular transport of anti-ICAM-1 NCs in vivo and then developed new cellular models expressing ICAM-1 from mouse, dog, pig, and monkey, species relevant to pharmaceutical translation and veterinary medicine. ICAM-1 expression was verified by flow cytometry and confocal microscopy. These cells showed specific targeting compared to IgG NCs or cells treated with anti-ICAM-1 blocker. Anti-ICAM-1 NCs entered cells in a time- and temperature-dependent manner, with kinetics and pathway compatible with CAM-mediated endocytosis. All parameters tested were strikingly similar to those from human cells expressing ICAM-1 endogenously. Therefore, this new cellular platform represents a valuable tool that can be used in parallel to support in vivo studies on ICAM-1-targeted NCs during pharmaceutical translation. |
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