Reversible encapsulations and stimuli-responsive biological delivery from a dynamically assembled cucurbit[7]uril host and nanoparticle guest scaffold.

The positive outcome of any therapeutic molecule requires control over its delivery rate. When delivered without control, administration of large doses is required to stimulate a therapeutic effect, frequently leading to increased toxicity or undesirable side effects. Recent advances introduced "smart" materials that actively release drugs in response to environmental stimuli. Although a variety of endogenous and exogenous triggers are reported, they are either difficult to control or lack tissue penetration depth. We report here a dynamic drug delivery scaffold based on a cucurbit[7]uril (CB[7]) host and benzylammonium functionalized gold nanoparticle (AuNP) guest that utilizes a bioorthogonal small molecule to achieve therapeutic control. In addition to their ability to reach deep tissue, small molecule activation is benefitted by their external controllability. Through cell culture studies we demonstrate that the host-guest supramolecular scaffold provides a nontoxic platform that effectively encapsulates a variety of therapeutic molecules and controls the payload release upon exposure to a high-affinity competitive guest molecule. This study presents a new strategy for controlling drug release rate through the use of competitive interactions of orthogonally presented guest molecules with immediate advantages in dosage control.