Multivalent ligand-receptor interactions constitute one of fundamental concepts underlying the design of multifunctional nanoparticles (NPs) in targeted drug delivery. This multivalent effect is not only responsible for high binding avidity but also proposed to confer a strong force of NP adhesion by which NPs remain bound tightly under a shear flow. Despite such significance, the correlation between avidity constants and adhesion forces remains poorly investigated, in part, due to the paucity of well-defined NP probes. Here we report multivalent dendrimer probes designed as tumor or bacteria-targeted NPs, and discuss two biophysical methods employed to investigate avidity-adhesion force distributions on model surfaces. These probes were designed by conjugating a ligand molecule to generation 5 (G5) PAMAM dendrimer, yielding G5(Ligand)n (n = mean valency). Each multivalent probe was investigated for its binding avidity to a model cell surface by surface plasmon resonance (SPR) spectroscopy. The same dendrimer conjugate was then used as an atomic force microscopy (AFM) probe to determine its physical force of adhesion to a model cell surface by single molecule force microscopy. We discuss the distribution of SPR avidity constants and corresponding AFM adhesion forces in response to ligand valency. In summary, this paper reports advances made in the design and biophysical characterization of multivalent dendrimer nanoprobes by SPR and AFM.

Assessment of binding avidity and adhesion forces by multivalent dendrimer nanoprobes

2019 Spring National Meeting

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