Combined antitumoral therapy with nanoassemblies of bolaform polyisoprenoyl paclitaxel/gemcitabine prodrugs

Abstract

We report here the design and synthesis of novel bolaform prodrugs in which the two headgroups are constituted of gemcitabine and/or paclitaxel anticancer drugs bound together through short polyisoprenoyl spacers. Thanks to the unique auto-assembling properties of the polyisoprenoyl linker, these bolaform prodrugs were found to self-assemble in aqueous media into 100–200 nm nanoassemblies. The synthesis of the prodrugs and the characterization of the nanoassemblies by DLS, TEM and cryoTEM are described. These gemcitabine/paclitaxel nanodevices with high drug payloads displayed improved in vitro activities on several human and murine cancer cell lines comparatively to nanoassemblies of the corresponding squalenoyl drugs alone or in combination.