Facile Preparation of Core-Crosslinked Micelles from Azide-Containing Thermoresponsive Double Hydrophilic Diblock Copolymer via Click Chemistry XIAOZE JIANG, JINGYAN ZHANG, YUEMING ZHOU, JIAN XU, SHIYONG LIU Department of Polymer Science and Engineering, Joint Laboratory of Polymer Thin Films and Solution, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China Received 27 August 2007; accepted 29 September 2007 DOI: 10.1002/pola.22430 Published online in Wiley InterScience (www.interscience.wiley.com). ABSTRACT: Double hydrophilic diblock copolymer, poly(N,N-dimethylacrylamide)-b- poly(N-isopropylacrylamide-co-3-azidopropylacrylamide) (PDMA-b-P(NIPAM-co-AzPAM), containing azide moieties in one of the blocks was synthesized via consecutive reversible addition-fragmentation chain transfer polymerization. The obtained diblock copoly- mer molecularly dissolves in aqueous solution at room temperature, and can further supramolecularly self-assemble into core-shell nanoparticles consisting of thermores- ponsive P(NIPAM-co-AzPAM) cores and water-soluble PDMA coronas above the lower critical solution temperature of P(NIPAM-co-AzPAM) block. As the micelle cores con- tain reactive azide residues, core crosslinking can be facilely achieved upon addition of difunctional propargyl ether via click chemistry. In an alternate approach in which the PDMA-b-P(NIPAM-co-AzPAM) diblock copolymer was dissolved in a common or- ganic solvent (DMF), the core-crosslinked (CCL) micelles can be fabricated via ‘‘click’’ crosslinking upon addition of propargyl ether and subsequent dialysis against water. CCL micelles prepared by the latter approach typically possess larger sizes and broader size distributions, compared with that obtained by the former one. In both cases, the obtained (CCL) micelles possess thermoresponsive cores, and the swelling/ shrinking of which can be finely tuned with temperature, rendering them as excellent candidates as intelligent drug nanocarriers. Because of the high efficiency and quite mild conditions of click reactions, we expect that this strategy can be generalized for the structural fixation of other self-assembled nanostructures. V V C 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 860–871, 2008 Keywords: block copolymers; reversible addition fragmentation chain transfer (RAFT); self-assembly; stimuli-sensitive polymers; supramolecular structures INTRODUCTION In selective solvents, block copolymers can self- assemble into various mesophases with diverse morphologies. 1–6 To enhance the structural in- tegrity of these supramolecular nanostructures such as block copolymer micelles, the methodol- ogy of covalent stabilization via core crosslink- ing 7–12 or shell crosslinking 13–20 have been extensively explored. The preparation of core- crosslinked (CCL) micelles can be further cate- gorized into two main strategies. In the first strategy, block copolymers con- taining polymerizable or crosslinkable groups were synthesized using controlled radical or Correspondence to: S. Liu (E-mail: sliu@ustc.edu.cn) Journal of Polymer Science: Part A: Polymer Chemistry, Vol. 46, 860–871 (2008) V V C 2007 Wiley Periodicals, Inc. 860