Force Spectroscopy of Multivalent Binding of Riboflavin-Conjugated
Dendrimers to Riboflavin Binding Protein
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Abstract
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)<sub><i>n</i></sub> nanoparticle. By varying the average RF
ligand valency (<i>n</i> = 0, 3, 5), the rupture force was
measured between G5(RF)<sub><i>n</i></sub> and the riboflavin
binding protein (RFBP). The rupture force increased when the valency
of RF increased. We observed at the higher valency (<i>n</i> = 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