Heat-Induced Living Crystallization-Driven Self-Assembly: The Effect of Temperature and Polymer Composition on the Assembly and Disassembly of Poly(2-oxazoline) Nanorods

Poly(2-oxazoline)s (POx) are promising biomaterials constituents as they display biocompatibility and versatile functionality while possessing tunable hydrophilicity and favorable physical properties. Recently we showed that POx nanorods of tunable length could be prepared with a hydrophilic and stealthy poly(2-methyl-2-oxazoline) (PMeOx) corona and a crystalline poly(2-isopropyl-2-oxazoline) (PiPrOx) core using a novel heat-induced living crystallization-driven self-assembly (CDSA) methodology [Chem. Sci. 2021, 12, 7350-7360]. Herein, the essential steps of heat-induced living CDSA were examined in detail. We report an improved method for POx nanorod seed preparation via ultrasonication above the BCP cloud point temperature, and study the effects of annealing temperature and polymer composition on the kinetics of POx nanorod seeded growth. From these observations we propose that an optimal balance of control over POx nanorod size and self-assembly rate can be achieved when seeded growth is performed at the block copolymer cloud point temperature. Unlike other crystalline-core polymer nanoparticles, the POx nanorods studied are not kinetically trapped under ambient conditions and are observed to slowly disassemble. A detailed study of this disassembly reveals a strong effect of storage temperature and polymer composition on the rate of dissolution, with lower temperatures and a shorter corona-forming block favoring faster dissolution. Finally, freeze-drying protocols are described that allow POx nanorod seeds and particles of defined length to be stored in the dried state. We believe that this report will serve as a useful guide for those seeking to prepare POx nanorods and to take advantage of their highly promising biomedical properties.