Cell Surface Decoration with Multivalent Host-Guest Dendrimers for Localized Drug Capture

Molecular-scale recognition motifs in drug delivery applications have emerged in recent decades to facilitate in situ recognition and complex formation under physiological conditions. Herein, a design utilizing host-guest supramolecular interactions from cucurbit[7]uril (CB[7]) to drive model prodrugs to the surface of NIH-3T3 cells is discussed. A combination of confocal imaging and flow cytometry presents results indicating clear cell membrane incorporation and retention of a single cholesterol moiety conjugated to a fully CB[7]-functionalized PAMAM dendrimer that can bind and capture administered Fc-N-Cy5 at cell surfaces over the course of 3 days in vitro. Dendrimer-modified cells administered with Fc-N-Cy5 showed nearly a two-order of magnitude increase in fluorescence intensity after 24 hours compared to unmodified cells washed with Fc-N-Cy5 under the same protocol. The results presented in this thesis offer exciting potential for improved drug delivery applications, in which the multivalency of the design could serve to increase the effective binding affinity of circulating prodrugs by enabling avidity and enhancing recognition specificity.