On the encapsulation and assembly of anticancer drugs in a cooperative fashion.

In this study, we report the remarkable recognition and assembly characteristics of symmetric basket containing two adjoining and nonpolar cavities with six biocompatible GABA residues at their northern and southern termini. From the results of experimental (H NMR, fluorescence and UV-Vis spectroscopies) and computational (MM-MC/OPLS3e) investigations, we deduced that hexaanionic captured two molecules of anticancer drug doxorubicin in water and accommodated them in its two deep cavities. The formation of stable ⊂ ( = 3 × 10 M) was accompanied by the exceptional homotopic cooperativity ( = 4 / = 112) in which = 3.2 ± 0.8 × 10 M and = 9 ± 1 × 10 M. Furthermore, bolaamphiphilic ⊂ assembled into spherical nanoparticles (DLS, -TEM and TEM) possessing 41% drug loading. The preorganization of abiotic receptor and its complementarity to have been proposed to play a part in the positive cooperativity in which ten favorable noncovalent contacts ( hydrogen bonds, salt bridges, C-H···π and π-π contacts) are formed between doxorubicin and the dual-cavity host. In the case of topotecan , however, the absence of multiple and favorable basket⊂drug interactions resulted in the predominant formation of a binary ⊂ complex ( = 2.12 ± 0.01 × 10 M) and the negative homotopic allostery ( ≪ 1). To summarize, our study lays out a roadmap for creating a family of novel, accessible and multivalent hosts capable of complexing anticancer agents in a cooperative manner. As basket⊂drug complexes organize into highly loaded nanoparticles, the reported soft material is amenable to the bottom-up construction of stimuli-responsive nanomedicine capable of effective scavenging and/or delivery of drugs.