Decahexanuclear Zinc(II) Coordination Container Featuring a Flexible Tetracarboxylate Ligand: A Self-Assembly Supermolecule for Highly Efficient Drug Delivery of Anti-Inflammatory Agents

The
application of a coordination container in biomedicine is hindered
by single binding domains and unsatisfactory biostability and biocompatibility.
Herein, we designed a sulfonylcalix[4]­arene-based decahexanuclear
zinc­(II) coordination container employing a flexible tetracarboxylate
ligand as a linker and utilized it as a novel drug delivery system.
The coordination container consisting of one endo and four exo cavities
provides multiple binding domains for efficient encapsulation of drug
molecules as clearly revealed by systematic host–guest studies
using NMR techniques of 1H NMR titration experiments and
2D NOESY and diffusion-ordered NMR spectroscopy studies. Incorporation
of a flexible p-phenylene-bis­(methanamino) spacer
into the container via the carboxylate linker allowed a stepwise drug
loading process through sequential binding at endo and exo cavities,
as well as enabling pH-responsive stepwise drug release. The drug-loaded
coordination container not only exhibits excellent biostability and
biocompatibility but also provides encouraging therapeutic efficiency
toward inflammatory macrophages as revealed by in vitro studies. The
novel strategy for engineering the endo cavity of a coordination container
provides a new approach to achieving controlled drug delivery and
opens up new opportunities for designing novel functional supramolecular
materials.