Engineering of pH-triggered nanoplatforms based on novel poly(2-methyl-2-oxazoline)-b-poly[2-(diisopropylamino)ethyl methacrylate] diblock copolymers with tunable morphologies for biomedical applications

Abstract

A two-step synthetic approach via the combination of living cationic ring-opening (CROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization techniques was used to produce novel amphiphilic block copolymers based on the water-soluble poly(2-methyl-2-oxazoline) (PMeOx), which holds protein repelling properties, linked to the hydrophilic–hydrophobic pH-responsive block poly[2-(diisopropylamino)ethyl methacrylate] (PDPA). Hydrodynamic flow focusing nanoprecipitation microfluidics (MF) was further employed to manufacture block copolymer self-assemblies. Interestingly, although all the synthesized macromolecules contained higher amounts of the pH-responsive segment, the microfluidic approach allowed the manufacturing of core–shell micelles and polymersomes. The morphology seems to be driven by the overall molecular weight of the block copolymers rather than by the hydrophilic-to-hydrophobic weight ratio. Longer and shorter amphiphilic chains enabled the manufacturing of core–shell assemblies and polymeric vesicles, respectively. The use of PMeOx and PDPA blocks confers serum stability and pH-responsive behavior to the nanoparticles in a pH window which is particularly useful for tumour detection and therapy. The self-assembled nanostructures are non-toxic even at fairly high polymer concentrations. All these features therefore can be useful in the design of pH-triggered nanoplatforms of distinct morphologies towards a variety of biomedical applications, for instance, the loading and delivery of hydrophobic and hydrophilic therapeutics.