Self-Assembling Prodrugs

Self-assembly of a simple molecular building unit can yield complex supramolecular architectures with new functions that the individual unit does not carry. This strategy has been used to create a plethora of interesting nanoscopic and microscopic morphologies from block copolymers, small molecular amphiphiles, peptides, proteins, and DNA. The specific control over size, shape, surface chemistry, and degradation kinetics enables supramolecular nanostructures the unique capacity for use as carriers to deliver therapeutic agents. In this carrier-cargo approach, the self-assembling units are typically biocompatible and biodegradable but biologically inert molecules that do not possess any function beyond ensuring the specific delivery and controlled release of the functional units. Our strategy presented here is to devise approaches that enable anticancer drugs to directly assemble into discrete well-defined nanostructures with the potential for self-delivery. In this presentation, I will detail our rational design of monodisperse, amphiphilic anticancer drugs—which we term drug amphiphiles (DAs)—that can spontaneously associate into discrete, stable supramolecular nanostructures with a 100% drug loading. Depending on the number and type of the drug in the molecular design, the resulting nanostructures could assume various morphologies. Our results suggest that formation of nanostructures provides protection for both the drug and the biodegradable linker from the external environment and offers a mechanism for controlled release.