Tuning the allosteric sequestration of anticancer drugs for developing cooperative nano-antidotes.

A dual-cavity basket 1(6-), holding six gamma-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 = 10(12) M-2) anthracycline complexes [(8(+)-11(+))(2)subset of 1(6-)], assembled into nanoparticles, occurred with positive homotropic cooperativity (alpha = 4K(2)/K-1 = 1.1 +/- 0.3 x 10(2)-1.3 +/- 0.7 x 10(3)) in PBS medium. Importantly, weakening the first binding event (K-1, i.e. by removing HBs) turned the second one (K-2) more favorable. The finding is of interest for developing cooperative nano-antidotes acting as biodetoxifying agents.