Polyion complex micelles possessing thermoresponsive coronas and their covalent core stabilization via click chemistry

Two oppositely charged graft ionorners, P(MAA-co-AzPMA)-g-PNIPAM and P(QDMA-co-AzPMA)-g-PNIPAM, containing thermosensitive PNIPAM graft chains were successfully synthesized via a combination of atom transfer radical polymerization (ATRP) and click reactions, where PAzPMA, PMAA, PNIPAM, and PQDMA are poly(3-azidopropyl methacrylate), poly(methacrylic acid), poly(N-isopropylacrylamide), and poly(2-(dimethylamino)ethyl methacrylate) (PDMA) fully quaternized with methyl iodide, respectively. In aqueous solution, polyelectrolyte, complexation between negatively charged backbone of P(MAA-co-AzPMA)g-PNIPAM and positively charged backbone of P(QDMA-co-AzPMA)-g-PNIPAM leads to the formation of polyion complex (PIC) micelles consisting of polyion complex cores and thermoresponsive PNIPAM coronas. Upon addition of a difunctional cross-linker, propargy ether, PIC micelles can be facilely cross-linked via click reactions. The obtained covalently core-stabilized PIC micelles exhibit permanent stability against the addition of NaCl and pH changes, which are drastically different from that of non-cross-linked PIC micelles. Moreover, these novel types of stable PIC micelles exhibit thermoinduced dispersion/aggregation due to the presence of PNIPAM coronas, suggesting that their physical affinity to external substrates can be tuned with temperature. They might act as stable nanocarriers of charged compounds or highly efficient nanoreactors of polar compounds in the field of pharmaceutical formulation or biotechnology.