Figure 5.

(A) Schematic illustration of polyprodrug unimolecular micelles with hyperbranched cores conjugated with gadolinium complex, reductive milieu-cleavable camptothecin prodrugs and hydrophilic coronas functionalized with guanidine residues. (B) T₁-weighted spin-echo MR images of (a) small molecule alkynyl-DOTA(Gd) (DOTA, tetraazacyclododecanetetraacetic acid) complex and hyperbranched polyprodrug amphiphilies (HPA) after incubating with various concentrations of DL-dithothreito (DTT) for 12 h. (C) Water proton longitudinal relaxation rates (1/T₁) of small molecule alkynyl-DOTA(Gd) complex and HPA after treating with DTT (0-20 mM). (D) MR images recorded for (a) untreated HepG2 cells, (b) HepG2 cells treated with HPA for 12 h, and (c) HepG2 cells pretreated with 10 mM GSH-OEt (GSH reduced ethyl ester) for 2 h to elevate intracellular GSH level, and then coincubated with HPA for 12 h. Reprinted with permission from ref. 77. Copyright 2015, American Chemical Society.