Tuning the allosteric sequestration of anticancer drugs for developing cooperative nano-antidotes†
A dual-cavity basket 16−, holding six γ-aminobutyric acids at its termini, encapsulates variously sized aromatics 2–7+, including four anthracyclines (8+–11+), driven by the hydrophobic effect and hydrogen bonding (HB). In particular, the formation of stable (K = 1012 M−2) anthracycline complexes [(8+–11+)2⊂16−], assembled into nanoparticles, occurred with positive homotropic cooperativity (α = 4K2/K1 = 1.1 ± 0.3 × 102–1.3 ± 0.7 × 103) in PBS medium. Importantly, weakening the first binding event (K1, i.e. by removing HBs) turned the second one (K2) more favorable. The finding is of interest for developing cooperative nano-antidotes acting as biodetoxifying agents.