ArticleJournal of drug delivery science and technology2024
New Cellular Models to Support Preclinical Studies on ICAM-1-Targeted Drug Delivery.
Article in Journal of drug delivery science and technology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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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