Putative
riboflavin receptors are considered as
biomarkers due to their overexpression in breast and
prostate cancers. Hence, these receptors can be potentially exploited for use in targeted drug delivery systems where
dendrimer nanoparticles with multivalent
ligand attachments can lead to greater specificity in cellular interactions. In this study, the single molecule force spectroscopy technique was used to assess the physical strength of multivalent interactions by employing a
riboflavin (RF)-conjugated generation 5
PAMAM dendrimer G5(RF)n nanoparticle. By varying the average RF
ligand valency (n = 0, 3, 5), the
rupture force was measured between G5(RF)n and the
riboflavin binding protein (RFBP). The
rupture force increased when the valency of RF increased. We observed at the higher valency (n = 5) three binding events that increased in
rupture force with increasing loading rate. Assuming a single energy barrier, the Bell-Evans model was used to determine the kinetic off-rate and barrier width for all binding interactions. The analysis of our results appears to indicate that multivalent interactions are resulting in changes to
rupture force and kinetic off-rates.