Origin of broad polydispersion in functionalized dendrimers and its effects on cancer cell binding affinity

TL;DR

This paper investigates the broad distribution of ligands on functionalized dendrimers and how this affects their ability to bind to cancer cells, revealing a cooperative conjugation process and a single desorption time constant.

Contribution

It introduces a model explaining ligand distribution broadness and binding dynamics, highlighting positive cooperativity and permanent surface attachment in dendrimers.

Findings

Ligand distribution broadness is due to positive cooperativity in conjugation.

Nanoparticles exhibit a single desorption time constant.

Surface-bound nanoparticles are permanently affixed.

Abstract

Nanoparticles with multiple ligands have been proposed for use in nanomedicine. The multiple targeting ligands on each nanoparticle can bind to several locations on a cell surface facilitating both drug targeting and uptake. Experiments show that the distribution of conjugated ligands is unexpectedly broad, and the desorption rate appears to depends exponentially upon the mean number of attached ligands. These two findings are explained with a model in which ligands conjugate to the nanoparticle with a positive cooperativity of $\approx 4kT$, and that nanoparticles bound to a surface by multiple bonds are permanently affixed. This drives new analysis of the data, which confirms that there is only one time constant for desorption, that of a nanoparticle bound to the surface by a single bond.