Amphiphilic triblock copolymers for combined therapy

Polymeric nanoparticles (NPs) play an important role in drug delivery as nanocarriers for small hydrophobic molecule drugs and as non-viral vectors for gene delivery [1] (plasmid DNA or siRNA). Combination of both properties in a single nanoparticle formulation can be useful in cancer treatment. In this topic, amphiphilic autoassembling block copolymers for realization of NPs offer a wide range of opportunities, due to the possibility of fine tuning the structure (nature, length and ratio of blocks) and surface properties of final NPs. In this work, synthesis and characterization of amphiphilic triblock copolymers based on polyethyleneglycol (PEG)-poly(dimethylaminoethyl-methacrylate) (pDMAEMA)-polycaprolactone (PCL) with different blocks length are described, with the aim to realize NPs for a combined anticancer therapy. The structure of triblock copolymers is shown in Figure 1. Figure 1 PEG was chosen as hydrophilic block for its stealth properties; pDMAEMA cationic block, intended for siRNA complexation, was synthesized via atom transfer radical polymerization (ATRP)[2]; finally, PCL was conjugated via "click" reaction through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) as biodegradable hydrophobic block. Copolymers were characterized through 1H-NMR, FTIR, GPC and DSC. NPs were obtained by nanoprecipitation and characterized for size, polydispersity index, surface charge and stability. Critical micellar concentrations (CMC) were determined. NPs were loaded with docetaxel (DTX), and a non-targeting pool siRNA was adsorbed by gentle stirring on DTX-loaded NPs. The complexes were characterized by electrophoresis on agarose gel. The final NPs showed narrow size distribution and good loading efficiency and release profiles.