Surface Ligand Valency and Immunoliposome Binding: when More Is Not Always Better

Area of Science:

• Nanotechnology
• Bioconjugation Chemistry
• Immunology

Background:

• Active targeting in nano-drug delivery relies on surface ligands like antibodies.
• Nanoparticle valency (ligand number) is crucial for targeting efficiency.
• Immunoliposomes (ILs) are models for studying antibody-mediated targeting.

Purpose of the Study:

• To investigate the correlation between IL valency and binding properties.
• To understand how valency influences the targeting of nano-drug delivery systems.
• To model the binding behavior of ILs with varying antibody densities.

Main Methods:

• Antibodies (anti-CD3 Fab) were conjugated to liposomes to create ILs.
• ILs were characterized to have 2-22 antibody copies per liposome.
• Biolayer Interferometry (BLI) measured IL binding to surfaces with varying antigen densities (CD3D/E).

Main Results:

• IL binding mode (monovalent vs. multivalent) depended on surface ligand density, not IL valency.
• IL valency correlated with dissociation rate (Koff) but not association rate (Kon).
• Increased IL valency did not necessarily enhance binding capabilities.

Conclusions:

• A model was proposed to explain IL binding properties based on valency and target antigen density.
• Binding modes adapt to antigen density on target surfaces.
• This model aids in designing optimized active targeting drug delivery systems.