The creation of vehicles for the effective delivery of hydrophobic anticancer drugs to tumor sites has garnered major attention in cancer chemotherapies for several decades. A successful strategy promises immense benefits to cancer sufferers through both the reduction of side effects and a greater treatment efficacy. Current approaches focus on the use of nanosized carriers, whereby the drug's pharmacokinetic properties and biodistribution profiles are manipulated by encapsulation within, or by conjugation to the carrier. While these methods can be effective, there are concerns regarding the short-term and long-term toxicities arising from the synthetic nanomaterials other than the drug being delivered. Furthermore, there are inherent difficulties in achieving a quantitative and high drug loading per carrier (typically less than 10%). 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 high and fixed drug loading. Depending on the number and type of the drug in the molecular design and also the chosen peptide sequence, the resulting nanostructures could assume various morphologies, such as nanofibers, nanotubes or toroids. Our results also suggest that formation of nanostructures provides protection for both the drug and the biodegradable linker from the external environment and thus offers a mechanism for controlled release.

Peptide-based drug amphiphiles for self-delivering supramolecular nanomedicine

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.