DOI: 10.1021/la902743y 2325 Langmuir 2010, 26(4), 2325–2332 Published on Web 10/15/2009 pubs.acs.org/Langmuir © 2009 American Chemical Society Thermoresponsive Vesicular Morphologies Obtained by Self-Assemblies of Hybrid Oligosaccharide-block-poly(N-isopropylacrylamide) Copolymer Systems Issei Otsuka, † Keita Fuchise, ‡ Sami Halila, † S ebastien Fort, † Karim Aissou, † Isabelle Pignot-Paintrand, † Yougen Chen, ‡ Atsushi Narumi, § Toyoji Kakuchi, ‡ and Redouane Borsali* ,† † Centre de Recherche sur les Macromol  ecules V eg etales (CERMAV, UPR-CNRS 5301) affiliated with Universit e Joseph Fourier and member of Institut de Chimie Mol  eculaire ICMG FR2607, BP53, 38041 Grenoble Cedex 9, France, ‡ Division of Biotechnology and Macromolecular Chemistry, Graduate School of Engineering, Hokkaido University, 060-8628 Sapporo, Japan, and § Department of Polymer Science and Engineering, Graduate school of Science and Engineering, Yamagata University, 992-8510 Yonezawa, Japan Received July 26, 2009. Revised Manuscript Received September 11, 2009 This work discusses the self-assembly properties of thermoresponsive hybrid oligosaccharide-block-poly(N-iso- propylacrylamide) copolymer systems: maltoheptaose-block-poly(N-isopropylacrylamide) (Mal 7 -b-PNIPAM n ) copo- lymers. Those systems at different molar masses and volume fractions were synthesized using Cu(I)-catalyzed 1, 3-dipolar azide/alkyne cycloaddition, so-called “click” chemistry, between an alkynyl-functionalized maltoheptaose (1) and poly(N-isopropylacrylamide) having a terminal azido group (N 3 -PNIPAM n ) prepared by atom transfer radical polymerization (ATRP). While the cloud point (T cp ) of the N 3 -PNIPAM n ranged from 36.4 to 51.5 °C depending on the degree of polymerization, those obtained of the diblock copolymers ranged from 39.4 to 73.9 °C. The self-assembly of such systems is favored due to the hydrophobicity of the PNIPAM in water above the T cp . While the N 3 -PNIPAM n present polydisperse globular shape with a mean diameter of 500 nm, well-defined vesicular morphologies with an approximate diameter of 300 nm are obtained in diblock copolymer systems. These results were obtained and confirmed using static and dynamic light scattering as well as imaging techniques such as transmission electron microscope experiments. Introduction The ability of amphiphilic block copolymers to self-assemble into nano-organized morphologies (micelles, vesicles, bilayers, etc.) in aqueous and organic media has been widely studied. 1-4 In recent years, the interest in the self-assembly at the nanoscale of “hybrid” block copolymers, based on a biodegradable natural block and a synthetic polymer block, has been growing for their potential applications in biomedical use, such as gene and drug deliveries. 5,6 Carbohydrates are one of the abundant raw materi- als for the natural block that show biodegradability, biocompat- ibility, and biorecognition ability. Although this topic is of great importance, there have been few reports on the synthesis of saccharide-based hybrid block copolymers involving different strategies. In the early 1980s, a pioneering study in this field was carried out by Ziegast and Pfannem€ uller on the synthesis of poly(ethylene oxide)-block-oligosaccharide structures by end-to- end coupling techniques. 7 Since then, several studies on the synthesis of block copolymers consisting of polysaccharides, such as dextran, 8-13 hyaluronan, 14,15 and amylose, 16-19 with several synthetic blocks have been reported, using enzymatic polymeri- zation, coupling techniques, and living radical polymerization. In recent years, there has been increasing interest in “click” chem- istry to design block copolymers. 20 For instance, Lecommandoux and co-workers reported a simple and versatile strategy for synthesizing block copolymers consisting of polysaccharides and polypeptides by using Cu(I)-catalyzed 1,3-dipolar azide/ alkyne cycloaddition. 13,15 This strategy has many advantages compared to the others, and more precisely, it circumvents the incompatibility problem between saccharides and other blocks in terms of low coupling reactivity. Because of the amphiphilic nature of these polysaccharide-based hybrid block copolymers, recent work highlights the existence of expected self-assembled nanoparticles: micellar or vesicular morphologies obtained both *Corresponding author: E-mail borsali@cermav.cnrs.fr; Fax +33 476 037 640. (1) Darling, S. B. Prog. Polym. Sci. 2007, 32, 1152–1204. (2) Rodrı´guez-Hern andez, J.; Ch ecot, F.; Gnanou, Y.; Lecommandoux, S. Prog. Polym. Sci. 2005, 30, 691–724. 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