Figure 4.
Supramolecular homing applied to therapeutic design. (a) Doxorubicin modified with a strong ferrocene guest through a hydrazone linkage (Fc-Hdz-Dox) as well as a control of doxorubicin modified with a hydrazone but lacking a CB[7]-binding guest (Me-Hdz-Dox). (b) Potency of doxorubicin and hydrazone conjugates in vitro in MDA-MB-231 cancer cells fit to a variable slope inhibitor vs response curve with least-squares fitting (R2 > 0.97 for all drugs). (c) Tumor model to evaluate supramolecular homing of Fc-Hdz-Dox compared to Me-Hdz-Dox following application of F127-CB[7]:PEG8-Fc hydrogel adjacent to a tumor prepared from MDA-MB-231 (luc+) cells. Tumors were induced and 14 days following induction the hydrogel was injected (day 0). Animal weights were tracked as was bioluminescent signal measured by imaging following administration of d-luciferin. Each line on the tumor signal plot represents a single mouse, with group averages noted by bold lines (*P < 0.05, **P < 0.01). All mice survived until the day 28 time point.