Single particle tracking to probe small molecule ligand-receptor interactions

Ligand-receptor interactions are a key bionanoscale recognition event in endocytosis, endosomal trafficking, and immune system responses. Small molecule ligand-receptor interactions are not well-studied and could elucidate why nanoparticles with small molecule targeting ligands are successful in vitro but not clinically. In this presentation, the effect of nanoparticle design on promoting successful targeting events was measured by analyzing the dynamics of small molecule ligand-receptor interactions. With folic acid-folate receptor alpha (FA-FOLR1) as a case study, single particle trajectories of FA-conjugated nanoparticles were tracked on SKOV-3 cancer cell membranes in vitro using differential interference contrast (DIC) microscopy. The trajectories were quantitatively categorized with mean square displacement analysis into diffusion modes. The distribution of diffusion modes can be correlated to the biological nature of FA-FOLR1 interactions. These results suggest that anisotropic nanoparticle shape and a short linker molecule connecting folic acid to the nanoparticle surface are key design considerations for nanoparticles with small molecule targeting ligands.