Engineering adhesion dynamics of targeted delivery carriers

Engineering adhesion dynamics of targeted delivery carriers

Targeted delivery of imaging or therapeutic agents to sites of disease holds tremendous potential to transform detection and treatment of various diseases, including atherosclerosis and cancer. However, this potential has remained largely untapped because molecularly-targeted agents have failed to provide sufficient delivery yield and/or specificity. Thus, new strategies are needed not just to improve targeting, but radically shift the paradigm. Nanomaterial carriers offer numerous advantages as a delivery platform, including high-loading capacity, protection, facile attachment of targeting moieties, favorable pharmacokinetics, and ability to enhance carrier adhesion through multivalent binding interactions. But to date targeted nanoparticle carriers have been developed simply from the standpoint of generating specificity by attaching to biological molecules such as antibodies. But adhesion within the vasculature is a dynamic process, and thus we believe that a kinetic treatment will be far more powerful.

In previous work, we developed a framework to study nanoparticle adhesion from a kinetic standpoint, including tools to properly assess multiple bond formation (multivalency), mass transport, and hydrodynamic force effects. We then utilized this framework to study the influence of numerous design parameters including the size of the nanoparticle carrier and binding properties of the targeting molecule. Counterintuitively, we found that targeting selectivity, which is the specific targeting of diseased cells versus specific targeting of normal cells, can be improved simply by decreasing binding efficiency.

• Targeting vascular inflammation
• Targeting cancer