We report on the design of multifunctional polymeric prodrugs composed of a taxane anti-cancer drug and a small molecule cancer cell targeted ligand. The first step in our design is the regioselective conjugation of a chain transfer agent for RAFT polymerization to the C2 position of paclitaxel or docetaxel. Conjugation is demonstrated for acid- and enzyme-responsive linker chemistry. Subsequent RAFT polymerization of a hydrophilic monomer yielded well-defined taxane-polymer conjugates with high drug loading, water solubility, and stability. Fluorescent labelling can readily be achieved by incorporation of a small fraction of a fluorescent monomer, which did not alter the physico-chemical properties of the resulting conjugates. The versatility of this approach was further demonstrated by end post-functionalization with a small molecule targeting ligand for prostate cancer. We demonstrated using in vitro conditions that these conjugates exhibit enhanced uptake by prostate cancer cells expressing PSMA. Conjugates are readily taken up into endosomes where native PTX is efficiently cleaved off and then reaches its subcellular target.

Well-defined targeted polymer-taxane prodrugs

253rd National Meeting (2017)

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