A ‘smart’ approach towards the formation of multifunctional nano-assemblies by simple mixing of block copolymers having a common temperature sensitive segment

A smart approach has been developed to form nanoassemblies with tunable shell's functions by simply mixing three different block copolymers with a common temperature-responsive segment at 25 °C. The formation of nanoassemblies and their thermodynamic stability are driven by the hydrophobic interaction of the common poly(N-isopropylacrylamide-co-N-(isobutoxymethyl)acrylamide) (P(NIPAAm-co-BMAAm)) segment which has a lower critical solution temperature (LCST) below 25 °C. Three series of copolymers with different polymer structures, acrylamide-type P(NIPAAm-co-N-(hydroxymethyl)acrylamide (HMAAm))-b-P(NIPAAm-co-BMAAm), poly(ethylene oxide) (PEO)-b-P(NIPAAm-co-BMAAm), and methacrylate-type poly(2-lactobionamidoethyl methacrylate) (PLAMA)-b-P(NIPAAm-co-HMAAm)-b-P(NIPAAm-co-BMAAm), were successfully polymerized by reversible addition–fragmentation chain transfer (RAFT) polymerization. Regardless of the block copolymer types the selected block copolymers successfully formed a stable core–shell assembly with the collapsed common segments forming the inner core by simple mixing in aqueous solutions. The size distributions were monodisperse and relatively narrow when all or two of these three block copolymers were mixed, while addition of free-copolymers without the common segment did not affect the assembly formation. The ratio of functional segments into shell could be easily tuned by changing the mixing ratio of three block copolymers. This system is highly expected to find use as smart nano-carriers for encapsulation, targeting, and triggered release of drug under control through a combination of temperature-responsive chains, accessible functionality, and choice of sugar moiety.