(393am) Synthesis, Self-Assembly and Biomedical Evaluation of Paclitaxel

Paclitaxel is a taxoid currently in clinical use to treat breast, prostate, ovarian and non-small-cell lung cancers. Despite its promising therapeutic potential, paclitaxel has very low solubility in water. We recently devised a new strategy to produce supramolecular prodrugs by conjugating a hydrophilic tumor targeting peptides with cleavable linkers onto a paclitaxel moiety. The resulting paclitaxel prodrugs can self assemble into filamentous nanostructures in water and under physiological conditions. The choices of the linker chemistry provide a mechanism to tune the release rate of paclitaxel in the presence of tumor progression related biomolecules, and the peptide segments can be used to control over the size and shape of the assembled nanostructures.  Our cytotoxicity results show that the paclitaxel prodrug presents a similar IC 50 against breast cancer cell lines to that of the pure paclitaxel. The low critical micellization concentration of the designed prodrug suggests these nanostructures will be very stable during the circulation.