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

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.