Tunable stimuli-responsive self-assembly system that forms and stabilizes nanoparticles by simple mixing and heating/cooling of selected block copolymers

We propose here a unique protocol to produce stimuli-responsive self-assemblies using two block copolymers, poly(N-isopropylacrylamide) (PNIPAAm)-b-P(NIPAAm-co-N-(hydroxymethyl)acrylamide (HMAAm)) and PNIPAAm-b-P(NIPAAm-co-sodium 2-acrylamido-2-methylpropane sulfonic acid (AMPS)). These block copolymers were synthesized by an atom transfer radical polymerization (ATRP) method. PNIPAAm was selected as the common block to trigger macromolecular assembly in an aqueous environment above the lower critical solution temperature (LCST). Stable core-shell assemblies were, therefore, produced only by mixing two block copolymers above the LCST of PNIPAAm (the first LCST) when the common blocks became hydrophobic. Upon heating above the LCST of P(NIPAAm-co-HMAAm) (the second LCST), the second block became dehydrated and the size growth of assemblies was observed. The P(NIPAAm-co-AMPS), however, still formed a hydrated shell that prevented further aggregation and precipitation due to electrostatic stabilization through the anionic groups of AMPS. In other words, nanoassemblies, assembled above the second LCST, could be stabilized at the desired size by P(NIPAAm-co-AMPS). The second LCST and the resulting nanoassemblies diameter were controlled by varying the HMAAm content. Nanoassemblies can also be reversibly disentangled at temperatures below the LCSTs, with recovery of soluble block copolymer chains. Thus, the proposed protocol enables the facile preparation of stimuli-responsive nanoassemblies and customization of their size by simple mixing and heating/cooling of the selected block copolymers. Using temperature as a single on-off parameter to induce self-assembly in water circumvents the need for using organic solvents. The system reported here may be potentially useful for a range of applications, including drug and gene delivery, biosensing, or separation of biological molecules.