Entropy-Driven Supramolecular Biomaterials Enabling Innovations in Drug and Cell Delivery

Supramolecular biomaterials exploiting rationally-designed non-covalent interactions exhibit many distinct properties that enable innovative approaches to drug delivery. For example, supramolecular interactions can be used to generate dynamically cross-linking polymer networks, yielding shear-thinning and self-healing hydrogels that exhibit viscoelastic mechanical properties similar to biological tissues and flow properties enabling minimally invasive implantation in the body though direct injection or catheter delivery. In this talk we will discuss the preparation, characterization and application of a class of physical hydrogels generated by non-covalent interactions between modified biopolymers (BPs) and nanoparticles (NPs). Owing to the dynamic, non-covalent interactions between the NPs and BPs, the hydrogels flow under applied stress and their mechanical properties recover completely within seconds when the stress is relaxed, demonstrating the shear-thinning and injectable nature of the materials. Moreover, these interactions have been shown to be entropically driven, causing these materials to elicit alternative temperature-dependent mechanical properties than those typically observed in physical hydrogels. Further, the hierarchical construction of these biphasic hydrogels allows for multiple therapeutics ranging form peptides to proteins to cells to be entrapped simultaneously and delivered over user-defined timeframes ranging from days to months. These materials have proven to be particularly promising as controlled delivery technologies in vaccines and cancer immunotherapies - applications where precise release of complex mixtures of compounds over prolonged timeframes is crucial. In particular, the use of these materials for the controlled delivery of CAR-T cells and stimulatory cytokines to improve treatment of solid tumors will be discussed. Overall, this presentation will demonstrate the utility of a supramolecular approach to the design of biomaterials affording unique opportunities in the controlled delivery of therapeutics.