Communications to the Editor Consecutive Morphological Transitions in Nanoaggregates Assembled from Amphiphilic Random Copolymer via Water-Driven Micellization and Light-Triggered Dissociation Feng Tian, † Yuanyuan Yu, † Changchun Wang,* ,† and Shu Yang* ,‡ Key Laboratory of Molecular Engineering of Polymers (Ministry of Education), Department of Macromolecular Science and AdVanced Materials Laboratory, Fudan UniVersity, Shanghai 200433, China, and Department of Materials Science and Engineering, UniVersity of PennsylVania, 3231 Walnut Street, Philadelphia, PennsylVania 19014 ReceiVed January 21, 2008 ReVised Manuscript ReceiVed April 2, 2008 The past decade of research has witnessed a significant progress in macromolecular self-assemblies, which offer a rich variety of morphologies and transitions. 1 Recently, potential applications in controlled drug encapsulation, circulation, and targeted release 2 have boosted new interests in the development of responsive polymer assemblies that could continuously change their morphologies in water, 3 in response to an external stimulus, such as pH 4 and temperature. 5 Most of the effort, however, has focused on the design of block copolymers with well-defined architectures and narrow polydispersity, which are often found synthetically challenging. In comparison, random copolymers with a wide range of chemical functionalities and compositions are readily available. Nevertheless, because of their ill-defined structures and broad polydispersity, little has been exploited of their assemblies in aqueous solution. Therefore, it will be intriguing to see whether it is possible to form well- ordered nanoassemblies from an amphiphilic random copolymer solution, which can undergo continuous morphological transi- tions. Moreover, once the desired nanoassembly is formed, it will be interesting to trigger its dissociation by an external stimulus for controlled release of encapsulants. Among various external stimuli, including pH, temperature, and ionic strength, light potentially offers better spatial and temporal control 6,7 such that the time and the site of release will be determined by when and where the irradiation light is applied. Herein, we report a study of continuous morphological transitions from spherical micelles, through hollow tubes and wormlike rods, to large vesicles in nanoaggregates self- assembled from photoresponsive amphiphilic random copoly- mer, DNQMA-HEMA (Scheme 1). Through esterification of the side chain hydroxyl groups, the hydrophilic poly(hydroxy- ethyl methacrylate) (PHEMA) backbone is partially and ran- domly modified by the hydrophobic, light-responsive 2-diazo- 1,2-naphthoquinone (DNQ) molecules. The micellization and transition are then triggered simply by adding water into the copolymer/DMF solution. Upon irradiation to UV light at 405 nm, large vesicles become increasingly hydrophilic with time and gradually dissociate into globular hydrogel particles in the aqueous solution (Scheme 1), releasing the encapsulated dye molecules. As shown in Figure 1a, upon exposure to UV light, hydrophobic DNQ undergoes the Wolff rearrangement to 3-indenecarboxylate (IC), thus dramatically increasing its hy- drophilicity. 8 On the basis of this photochemical reaction, we incorporated DNQ molecules to the hydrophilic PHEMA side chains (Figure 1b). The resulting DNQ-modified photorespon- sive amphiphilic random copolymer has M w ) 3.1 × 10 5 g mol -1 and polydispersity (PDI) of ∼1.5 after three times dissolution-precipitation cycles. The average number of DNQ molecules attached to PHEMA side chains was estimated as ∼25 mol % by 1 H NMR. Detailed synthesis and characterization about the random copolymer can be found in the Supporting Information (Figure S1-Figure S4). To investigate the nature of the DNQ attachment, randomly or blocky, we performed DSC study and attempted homopolymerization from DNQ function- alized HEMA monomers. A single glass transition at 36.9 °C was observed (Figure S3), which was lower than the T g of PHEMA, 51.1 °C, suggesting that the DNQ moieties are randomly attached to the PHEMA side chains rather than formed a segregated block which is bound to have two distinctive transitions. In addition, we also found no homopolymerization from DNQ functionalized HEMA monomer via free radical * Corresponding authors. E-mail: ccwang@fudan.edu.cn; shuyang@ seas.upenn.edu. † Fudan University. ‡ University of Pennsylvania. Volume 41, Number 10 May 27, 2008  Copyright 2008 by the American Chemical Society 10.1021/ma800142j CCC: $40.75  2008 American Chemical Society Published on Web 05/02/2008