Multivalent Cucurbituril Dendrons for Cell Membrane Engineering with Supramolecular Receptors

The affinity possible from certain supramolecular motifs rivals that for some of the best-recognized interactions in biology. Cucurbit[7]­uril (CB[7]) macrocycles, for example, are capable of achieving affinities in their binding to certain guests that rival that of biotin–avidin. Supramolecular host–guest recognition between CB[7] and certain guests has been demonstrated to spatially localize guest-linked agents to desired sites in vivo, offering opportunities to better exploit this affinity axis for applications in biomedicine. Herein, architectures of CB[7] are prepared from a polyamidoamine (PAMAM) dendrimer scaffold, installing a PEG-linked cholesterol anchor on the opposite end of the dendron to facilitate cell membrane integration. Cells are then modified with this dendritic CB[7] construct in vitro, demonstrating the ability to deliver a model guest-linked agent to the cell membrane. This approach to realize synthetic supramolecular “membrane receptors” may be leveraged in the future for in situ imaging or modulation of cell-based therapies or to facilitate a synthetic supramolecular recognition axis on the cell membrane.