Controlling amphiphilic copolymer self-assembly morphologies based on macrocycle/anion recognition and nucleotide-induced payload release.

We report here a new approach to creating diversiform copolymer-derived self-assembly morphologies that relies on macrocycle/anion recognition in aqueous media. This approach exploits the anion binding features of a water-soluble form of the so-called 'Texas-sized' molecular box. When this tetracationic receptor is added to an aqueous solution of an amphiphilic copolymer bearing tethered carboxylate anion substituents, binding occurs to form a macrocycle/polymer complex. As the concentration of the box-like receptor increases, the relative hydrophilic fraction of the copolymer complex likewise increases. This leads to changes in the overall morphology of the self-assembled ensemble. The net result is an environmentally controllable system that mimics on a proof-of-concept level the structural evolution of organelles seen in living cells. The macrocycle/anion interactions respond in differing degrees to three key biological species, namely ATP, ADP, and AMP, which may be used as "inputs" to induce disassembly of these vehicles. As a result of this triggering and the nature of the morphological changes induced, the present copolymer system is capable of capturing and releasing in controlled manner various test payloads, including hydrophobic and hydrophilic fluorophores. The copolymer displays low inherent cytotoxicity as inferred from cell proliferation assays involving the HUVEC and HepG2 cell lines.