New Cellular Models to Support Preclinical Studies on ICAM-1-Targeted Drug Delivery.

Area of Science:

• Biomedical Engineering
• Cell Biology
• Drug Delivery

Background:

• Intercellular adhesion molecule 1 (ICAM-1) is a cell-surface protein targeted for drug delivery.
• Anti-ICAM-1 nanocarriers (NCs) show promise but their behavior in animal cells is not well understood due to species-specific ICAM-1 differences.

Purpose of the Study:

• To investigate the cellular uptake and transport mechanisms of anti-ICAM-1 nanocarriers in animal cells.
• To develop and validate novel cellular models expressing ICAM-1 from relevant animal species for pharmaceutical translation.

Main Methods:

• Qualitative in vivo assessment of anti-ICAM-1 NC transport.
• Development of cell lines expressing ICAM-1 from mouse, dog, pig, and monkey.
• Verification of ICAM-1 expression using flow cytometry and confocal microscopy.
• Assessment of NC uptake kinetics and temperature dependence.

Main Results:

• Targeted uptake of anti-ICAM-1 NCs was observed in engineered animal cell lines, distinct from control IgG NCs.
• NC internalization exhibited time- and temperature-dependent kinetics consistent with CAM-mediated endocytosis.
• Cellular transport parameters in animal cells closely mirrored those in human cells expressing ICAM-1.

Conclusions:

• The developed cellular models accurately mimic ICAM-1-mediated nanocarrier uptake in various species.
• This platform is a valuable tool for parallel in vivo and in vitro studies of ICAM-1-targeted nanocarriers.
• Findings support the use of anti-ICAM-1 nanocarriers in pharmaceutical translation and veterinary medicine.