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.

Supramolecular "Click Chemistry" for Targeting in the Body.

The fields of precision imaging and drug delivery have revealed a number of tools to improve target specificity and increase efficacy in diagnosing and treating disease. Biological molecules, such as antibodies, continue to be the primary means of assuring active targeting of various payloads. However, molecular-scale recognition motifs have emerged in recent decades to achieve specificity through the design of interacting chemical motifs. In this regard, an assortment of bioorthogonal covalent conjugations offer possibilities for in situ complexation under physiological conditions. Herein, a related concept is discussed that leverages interactions from noncovalent or supramolecular motifs to facilitate in situ recognition and complex formation in the body. Classic supramolecular motifs based on host-guest complexation offer one such means of facilitating recognition. In addition, synthetic bioinspired motifs based on oligonucleotide hybridization and coiled-coil peptide bundles afford other routes to form complexes in situ. The architectures to include recognition of these various motifs for targeting enable both monovalent and multivalent presentation, seeking high affinity or engineered avidity to facilitate conjugation even under dilute conditions of the body. Accordingly, supramolecular "click chemistry" offers a complementary tool in the growing arsenal targeting improved healthcare efficacy.