Modular Metal–Organic Polyhedra Superassembly: From Molecular-Level Design to Targeted Drug Delivery

Targeted drug delivery remains at the forefront of biomedical research but remains a challenge to date. Herein, the first superassembly of nanosized metal–organic polyhedra (MOP) and their biomimetic coatings of lipid bilayers are described to synergistically combine the advantages of micelles and supramolecular coordination cages for targeted drug delivery. The superassembly technique affords unique hydrophobic features that endow individual MOP to act as nanobuilding blocks and enable their superassembly into larger and well-defined nanocarriers with homogeneous sizes over a broad range of diameters. Various cargos are controllably loaded into the MOP with high payloads, and the nanocages are then superassembled to form multidrug delivery systems. Additionally, functional nanoparticles are introduced into the superassemblies via a one-pot process for versatile bioapplications. The MOP superassemblies are surface-engineered with epidermal growth factor receptors and can be targeted to cancer cells. In vivo studies indicated the assemblies to have a substantial circulation half-life of 5.6 h and to undergo renal clearance—characteristics needed for nanomedicines.