Microparticle adhesive dynamics and rolling mediated by selectin-specific antibodies under flow

Area of Science:

• Biomedical Engineering
• Immunology
• Vascular Biology

Background:

• Targeting inflamed endothelium is crucial for drug delivery and diagnostics.
• Selectins (E- and P-selectin) are key adhesion molecules on inflamed vascular endothelium.
• Developing effective microparticle-based targeting strategies remains a challenge.

Purpose of the Study:

• To evaluate the performance of microparticles functionalized with specific antibodies for targeting E- and P-selectin on inflamed endothelium.
• To compare the binding and adhesion capabilities of different antibody conjugates under flow conditions.

Main Methods:

• In vitro flow chamber studies using immobilized E- and P-selectin.
• Perfusion of 6-micron polystyrene microparticles conjugated with antibodies (HuEP5C7.g2 and G1), peptides, or carbohydrates.
• Assessment of leukocyte-like rolling and adhesion at venular shear rates.

Main Results:

• Microparticles conjugated with HuEP5C7.g2 (HuEP) demonstrated leukocyte-like rolling and transient adhesion.
• A higher affinity antibody (G1) alone failed to form bonds at venular flow rates.
• Co-conjugation of HuEP and G1 enabled stable adhesion by facilitating initial binding via HuEP.
• HuEP-conjugated microparticles showed superior binding under flow compared to previously characterized monoclonal antibodies.

Conclusions:

• HuEP is a promising alternative to natural ligands for targeting microparticles to inflamed endothelium.
• This strategy may enhance the delivery of therapeutic or diagnostic agents to inflamed vascular sites.
• Further development could optimize microparticle-based targeting for clinical applications.